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  • Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-22
    Mingge Ding; Chaoyang Liu; Rui Shi; Mingzhe Yu; Ke Zeng; Junjun Kang; Feng Fu; Mantian Mi

    Imbalanced mitochondrial dynamic including suppressed mitochondrial fusion has been observed in diabetic hearts. However, it is still unknown whether mitochondrial fusion promoter is an effective protection to diabetic hearts. This study was designed to explore the efficacy of mitochondrial fusion promoter on diabetic cardiomyopathy (DCM).

    更新日期:2020-01-23
  • Alterations of Nedd4‐2‐binding capacity in PY‐motif of NaV1.5 channel underlie long QT syndrome and Brugada syndrome
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-21
    Ya Wang; Yuan Du; Ling Luo; Peijing Hu; Guodong Yang; Tao Li; Xiu Han; Aiqun Ma; Tingzhong Wang

    Pathogenic variants of the SCN5A gene can cause Brugada syndrome (BrS) and long QT syndrome (LQTS), which predispose individuals to potentially fatal ventricular arrhythmias and sudden cardiac death. SCN5A encodes the NaV1.5 protein, the pore forming α‐subunit of the voltage‐dependent cardiac Na+ channel. Using a WW domain, the E3 ubiquitin ligase Nedd4‐2 binds to the PY‐motif ([L/P]PxY) within the C‐terminus of NaV1.5, which results in decreased protein expression and current through NaV1.5 ubiquitination. Here, we investigate the role of E3 ubiquitin ligase Nedd4‐2‐mediated NaV1.5 degradation in the pathological mechanisms of the BrS‐associated variant SCN5A‐p.L1239P and LQTS‐associated variant SCN5A‐p.Y1977N.

    更新日期:2020-01-23
  • Regulation and function of extra‐SCN circadian oscillators in the brain
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-22
    Kimberly Begemann; Anne‐Marie Neumann; Henrik Oster

    Most organisms evolved endogenous, so called circadian clocks as internal timekeeping mechanisms allowing them to adapt to recurring changes in environmental demands brought about by 24‐hour rhythms such as the light‐dark cycle, temperature variations, or changes in humidity. The mammalian circadian clock system is based on cellular oscillators found in all tissues of the body that are organized in a hierarchical fashion. A master pacemaker located in the suprachiasmatic nucleus (SCN) synchronizes peripheral tissue clocks and extra‐SCN oscillators in the brain with each other and with external time. Different time cues (so called Zeitgebers) such as light, food intake, activity, and hormonal signals reset the clock system through the SCN or by direct action at the tissue clock level. While most studies on non‐SCN clocks so far have focused on peripheral tissues, several extra‐SCN central oscillators were characterized in terms of circadian rhythm regulation and output. Some of them are directly innervated by the SCN pacemaker, while others receive indirect input from the SCN via other neural circuits or extra‐brain structures. The specific physiological function of these non‐SCN brain oscillators as well as their role in the regulation of the circadian clock network remains understudied. In this review we summarize our current knowledge about the regulation and function of extra‐SCN circadian oscillators in different brain regions and devise experimental approaches enabling us to unravel the organization of the circadian clock network in the central nervous system.

    更新日期:2020-01-23
  • The hypoxia tolerance of eight related African mole‐rat species rivals that of naked mole‐rats, despite divergent ventilatory and metabolic strategies in severe hypoxia
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-21
    Catherine M. Ivy; Ryan J. Sprenger; Nigel C. Bennett; Barry van Jaarsveld; Daniel W. Hart; Alexia M. Kirby; Dadmehr Yaghoubi; Kenneth B. Storey; William K. Milsom; Matthew E. Pamenter

    Burrowing mammals tend to be more hypoxia tolerant than non‐burrowing mammals and rely less on increases in ventilation and more on decreases in metabolic rate to tolerate hypoxia. Naked mole‐rats (Heterocephalus glaber, NMRs), eusocial mammals that live in large colonies, are among the most hypoxia‐tolerant mammals, and rely almost solely on decreases in metabolism with little change in ventilation during hypoxia. We hypothesized that the remarkable hypoxia tolerance of NMRs is an evolutionarily conserved trait derived from repeated exposure to severe hypoxia owing to their burrow environment and eusocial colony organization.

    更新日期:2020-01-22
  • Overexpression of the histidine triad nucleotide‐binding protein 2 protects cardiac function in the adult mice after acute myocardial infarction
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-21
    Mengkang Fan; Zhangwei Chen; Yin Huang; Yan Xia; Ao Chen; Danbo Lu; Yuan Wu; Ning Zhang; Peipei Zhang; Su Li; Jinxiang Chen; Yingmei Zhang; Aijun Sun; Yunzeng Zou; Kai Hu; Juying Qian; Junbo Ge

    To explore the role of the histidine triad nucleotide‐binding 2 (HINT2) protein in heart failure.

    更新日期:2020-01-22
  • Probing renal blood volume with magnetic resonance imaging
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-17
    Thoralf Niendorf; Erdmann Seeliger; Kathleen Cantow; Bert Flemming; Sonia Waiczies; Andreas Pohlmann

    Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T2*) in vivo, and is non‐invasive and indicative of renal tissue oxygenation. However, the renal T2* to tissue pO2 relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI‐based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T2* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol‐enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI‐based assessment of renal BVf.

    更新日期:2020-01-21
  • Aberrant sinus node firing during β‐adrenergic stimulation leads to cardiac arrhythmias in diabetic mice
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-18
    Anniek F. Lubberding; Laetitia Pereira; Jianbin Xue; Lisa A. Gottlieb; Vladimir V. Matchkov; Ana M. Gomez; Morten B. Thomsen

    Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type‐2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse model of T2DM and physiologically probed their underlying cause.

    更新日期:2020-01-21
  • Bradykinin – from snake poison to therapeutic options
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-16
    Philipp Hillmeister; Anja Bondke Persson

    The ancient Greek god Asclepius and his serpent‐entwined rod are well known among physicians and still associated with present‐day medicine and health care 1. Different origins and meanings are attributed to the snake rod symbol, and of particular significance is the belief that the snake symbol expresses the dual nature of the work of the physician, e.g. in the context of therapeutic drug use.

    更新日期:2020-01-17
  • Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-16
    Benjamin Portal; Sarah Delcourte; Renaud Rovera; Camille Lejards; Sebastien Bullich; Cécile E. Malnou; Nasser Haddjeri; Nicole Déglon; Bruno P. Guiard

    Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available psychotropic drugs is still unknown.

    更新日期:2020-01-16
  • Nitric oxide: to be or not to be an endocrine hormone?
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-16
    Zahra Bahadoran; Mattias Carlström; Parvin Mirmiran; Asghar Ghasemi

    Nitric oxide (NO), a highly‐reactive gasotransmitter, is critical for a number of cellular processes and has multiple biological functions. Due to its limited lifetime and diffusion distance, NO has been mainly believed to act in autocrine/paracrine fashion. The increasingly recognized effects of pharmacologically delivered and endogenous NO at a distant site, have changed the conventional wisdom and introduced NO as an endocrine signaling molecule. The notion is greatly supported by the detection of a number of NO adducts and their circulatory cycles, which in turn contribute to the transport and delivery of NO bioactivity, remote from the sites of its synthesis. The existence of endocrine sites of synthesis, negative feedback regulation of biosynthesis, integrated storage and transport systems, having an exclusive receptor, i.e. soluble guanylyl cyclase (sGC), and organized circadian rhythmicity, make NO something beyond a simple autocrine/paracrine signaling molecule that could qualify for being an endocrine signaling molecule. Here, we discuss hormonal features of NO from the classical endocrine point of view and review available knowledge supporting NO as a true endocrine hormone. This new insight can provide a new framework within which to reinterpret NO biology and its clinical applications.

    更新日期:2020-01-16
  • Fasting‐ and ghrelin‐induced food intake is regulated by NAMPT in the hypothalamus
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-14
    Roldan M. de Guia; Anna S. Hassing; Louise J. Skov; Cecilia Ratner; Kaja Plucińska; Søren Madsen; Thi A. Diep; Gelo V. Dela Cruz; Samuel A.J. Trammell; Elahu G. Sustarsic; Brice Emanuelli; Matthew P. Gillum; Zach Gerhart‐Hines; Birgitte Holst; Jonas T. Treebak

    Neurons in the arcuate nucleus of the hypothalamus are involved in regulation of food intake and energy expenditure, and dysregulation of signalling in these neurons promotes development of obesity. The role of the rate‐limiting enzyme in the NAD+ salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), for regulation energy homeostasis by the hypothalamus has not been extensively studied.

    更新日期:2020-01-14
  • Epac1 null mice have nephrogenic diabetes insipidus with deficient cortico‐papillary osmotic gradient and weaker collecting duct tight junctions
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-13
    Kathrine Sivertsen Åsrud; Ronja Bjørnstad; Reidun Kopperud; Line Pedersen; Barbara van der Hoeven; Tine Veronica Karlsen; Cecilie Brekke Rygh; Fitz‐Roy Curry; Marit Bakke; Rolf K. Reed; Olav Tenstad; Stein Ove Døskeland

    The cAMP‐mediator Epac1 (RapGef3) has high renal expression. Preliminary observations revealed increased diuresis in Epac1‐/‐ mice. We hypothesized that Epac1 could restrict diuresis by promoting trans‐cellular collecting duct water and urea transport or by stabilizing CD para‐cellular junctions to reduce osmolyte loss from the renal papillary interstitium.

    更新日期:2020-01-14
  • Adaptation of the cardiovascular system to weightlessness: Surprises, paradoxes and implications for deep space missions
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-13
    Peter Norsk

    Weightlessness in space induces a fluid shift from the dependent to the cephalad parts of the body leading to distension of the cardiac chambers and an accumulation of blood in the veins of the head and neck. Surprisingly, central venous pressure (CVP) during the initial hours of spaceflight decreases compared to being horizontal supine on the ground. The explanation is that the thorax is expanded by weightlessness leading to a decrease in inter‐pleural pressure (IPP), which exceeds the measured decrease in CVP. Thus, transmural CVP (TCVP = CVP − IPP) is increased indicating an augmented cardiac preload. Simultaneously, stroke volume and cardiac output (CO) are increased by 18%‐26% within the initial weeks and more so by 35%‐56% during the subsequent months of flight relative to in the upright posture on the ground. Mean arterial pressure (MAP) is decreased indicating a lower systemic vascular resistance (MAP/CO). It is therefore a surprise that sympathetic nerve activity is not suppressed in space and thus cannot be a mechanism for the systemic vasodilation, which still needs to be explored. Recent observations indicate that the fluid shift during long duration (months) flights is associated with increased retinal thickness that sometimes leads to optical disc oedema. Ocular and cerebral structural changes, increases in left atrial size and decreased flows with thrombi formation in the left internal jugular vein have also been observed. This is of concern for future long duration deep space missions because the health implications are unknown.

    更新日期:2020-01-13
  • BGP‐15: a potential therapeutic agent for critical illness myopathy
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-11
    Takashi Yamada

    In the current issue of Acta Physiologica, Larsson and colleagues examined the effect of chaperone co‐inducer BGP‐15 on impaired contractile function of the slow‐twitch soleus muscles in a rat intensive care unit (ICU) model.1 They found that BGP‐15 improves myofibrillar function in the soleus muscle after 5 days exposure to the ICU condition, which is accompanied by improved mitochondrial morphology/biogenesis and reduced oxidative post‐translational modifications (PTMs) of myosin molecules.

    更新日期:2020-01-13
  • In vivo hyperglycaemia exposure elicits distinct period‐dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress
    Acta Physiol. (IF 5.868) Pub Date : 2020-01-08
    Thomas A. Legøy; Luiza Ghila; Heidrun Vethe; Shadab Abadpour; Andreas F. Mathisen; Joao A. Paulo; Hanne Scholz; Helge Ræder; Simona Chera

    The loss of insulin‐secreting β‐cells, ultimately characterizing most diabetes forms, demands the development of cell replacement therapies. The common endpoint for all ex vivo strategies is transplantation into diabetic patients. However, the effects of hyperglycaemia environment on the transplanted cells were not yet properly assessed. Thus, the main goal of this study was to characterize global effect of brief and prolonged in vivo hyperglycaemia exposure on the cell fate acquisition and maintenance of transplanted human pancreatic progenitors.

    更新日期:2020-01-09
  • Altered mitochondrial metabolism in the insulin‐resistant heart
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-30
    Marina Makrecka‐Kuka; Edgars Liepinsh; Andrew J. Murray; Hélène Lemieux; Maija Dambrova; Kersti Tepp; Marju Puurand; Tuuli Käämbre; Woo H. Han; Paul de Goede; Katie A. O'Brien; Belma Turan; Erkan Tuncay; Yusuf Olgar; Anabela P. Rolo; Carlos M. Palmeira; Neoma T. Boardman; Rob C. I. Wüst; Terje S. Larsen

    Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

    更新日期:2019-12-30
  • Muscle unloading: A comparison between spaceflight and ground‐based models
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-30
    Rizwan Qaisar; Asima Karim; Adel B. Elmoselhi

    Prolonged unloading of skeletal muscle, a common outcome of events such as spaceflight, bed rest and hindlimb unloading, can result in extensive metabolic, structural and functional changes in muscle fibres. With advancement in investigations of cellular and molecular mechanisms, understanding of disuse muscle atrophy has significantly increased. However, substantial gaps exist in our understanding of the processes dictating muscle plasticity during unloading, which prevent us from developing effective interventions to combat muscle loss. This review aims to update the status of knowledge and underlying mechanisms leading to cellular and molecular changes in skeletal muscle during unloading. We have also discussed advances in the understanding of contractile dysfunction during spaceflights and in ground‐based models of muscle unloading. Additionally, we have elaborated on potential therapeutic interventions that show promising results in boosting muscle mass and strength during mechanical unloading. Finally, we have identified key gaps in our knowledge as well as possible research direction for the future.

    更新日期:2019-12-30
  • Effect of BIN1 on cardiac dysfunction and malignant arrhythmias
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-26
    Xiao‐Xin Jiang; Yan‐Rong Zhu; Hong‐Ming Liu; Shao‐Liang Chen; Dai‐Min Zhang

    Heart failure (HF) is the end‐stage syndrome for most cardiac diseases, and the 5‐year morbidity and mortality of HF remain high. Malignant arrhythmia is the main cause of sudden death in the progression of HF. Recently, bridging integrator 1 (BIN1) was discovered as a regulator of transverse tubule function and calcium signalling in cardiomyocytes. BIN1 downregulation is linked to abnormal cardiac contraction, and it increases the possibility of malignant arrhythmias preceding HF. Because of the detectability of cardiac BIN1 in peripheral blood, BIN1 may serve as a predictor of HF and may be useful in therapy development. However, the mechanism of BIN1 downregulation in HF and how BIN1 regulates normal cardiac function under physiological conditions remain unclear. In this review, recent progress in the biological studies of BIN1‐related cardiomyocytes and the effect of cardiac dysfunction and malignant arrhythmia will be discussed.

    更新日期:2019-12-27
  • Chaperone co‐inducer BGP‐15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-18
    Nicola Cacciani; Heba Salah; Meishan Li; Hazem Akkad; Anders Backeus; Yvette Hedstrom; Bhanu P. Jena; Jonas Bergquist; Lars Larsson

    Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co‐inducer BGP‐15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP‐15 on a limb muscle (soleus muscle) in response to the ICU condition.

    更新日期:2019-12-19
  • Sodium retention by uPA‐plasmin‐ENaC in nephrotic syndrome The authors reply
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-16
    Gitte R. Hinrichs; Kathrin Weyer; Ulla G. Friis; Per Svenningsen; Ida Katrine Lund; Rikke Nielsen; Géraldine Mollet; Corinne Antignac; Claus Bistrup; Boye L. Jensen; Henrik Birn

    There is a great interest in exploring the mechanisms of oedema in nephrotic syndrome (NS) as evidenced by 2 parallel studies published in Acta Physiologica (1, 2). This has generated an editorial comment (3) which we respond to by this rebuttal. The interest in the nephrotic edema reflects not only the significant negative impact this has on the quality of life, but also the difficulties associated with identifying optimal treatment due to the lack of pathophysiological insight.

    更新日期:2019-12-18
  • Ca2+‐independent and voltage‐dependent exocytosis in mouse chromaffin cells
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-11
    José Moya‐Díaz; Lucas Bayonés; Mauricio Montenegro; Ana M. Cárdenas; Henner Koch; Atsushi Doi; Fernando D. Marengo

    It is widely accepted that the exocytosis of synaptic and secretory vesicles is triggered by Ca2+ entry through voltage‐dependent Ca2+ channels. However, there is evidence of an alternative mode of exocytosis induced by membrane depolarization but lacking Ca2+ current and intracellular Ca2+ increase. In this work we investigated if such a mechanism contributes to secretory vesicle exocytosis in mouse chromaffin cells.

    更新日期:2019-12-13
  • Estimation of p70S6K Thr389 and 4E‐BP1 Thr37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-05
    Emil Rindom, Anders M Kristensen, Kristian Overgaard, Kristian Vissing, Frank Vincenzo de Paoli

    In a letter to the editor by Figureiredo et al1, entitled “On the appropriateness of antibody selection to estimate mTORC1 activity”, the authors question our choice of mTORC1 biomarkers2. We much appreciate the input and the possibility to emphasize our conclusions.

    更新日期:2019-12-05
  • Rebuttal to Editorial: sodium retention by uPA in nephrotic syndrome?
    Acta Physiol. (IF 5.868) Pub Date : 2019-12-03
    Bernhard N. Bohnert, Sandip Kanse, Silke Haerteis, Christoph Korbmacher, Ferruh Artunc

    We welcome the opportunity to reply to the elegant editorial of Prof. Ehmke 1 in which he highlights contradicting conclusions reached by Hinrichs et al. 2 and by us 3 in two recently published articles in Acta Physiologica. In our reply, we first comment on some technical aspects discussed by Prof. Ehmke as possible explanations for the discrepant conclusions reached in the two studies. In addition, we highlight some in vivo data reported by Hinrichs et al. 2 which in our view do not oppose but rather support our conclusion that urokinase, also known as urokinase‐type plasminogen activator (uPA), is not essential for sodium retention in nephrotic syndrome.

    更新日期:2019-12-03
  • The air that we breeze: From “Noble” discoveries of a general oxygen sensing principle to its clinical use
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-22
    Thomas Kietzmann

    Humans are obligate aerobic organisms that need air for life. The utmost importance of air for life has already been recognized thousands of years ago and is still evident in aspects of the ancient Greek medicine where blood was the humor associated with air. However, only a fraction, namely the ~20% of oxygen, constitutes the vital part from the air that we breeze. In the cell, oxygen is required for several enzymatic reactions and necessary to drive vital processes such as cellular respiration in which cells metabolize nutrients like sugars, proteins, or fat to obtain cellular energy in form of adenosine triphosphate (ATP).

    更新日期:2019-11-22
  • Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-31
    Este Leidmaa, Mary Gazea, Alexandre V. Patchev, Anna Pissioti, Nils Christian Gassen, Mayumi Kimura, Zsolt Liposits, Imre Kallo, Osborne F. X. Almeida

    Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals.

    更新日期:2019-11-18
  • Adipocyte‐derived extracellular vesicles modulate appetite and weight through mTOR signalling in the hypothalamus
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-27
    Jie Gao, Xinyu Li, You Wang, Yan Cao, Dengju Yao, Lijie Sun, Lv Qin, Hui Qiu, Xiaorong Zhan

    Type 2 diabetes and obesity are diseases related to surplus energy in the body. Abnormal interaction between the hypothalamus and adipose tissues is a key trigger of energy metabolism dysfunction. Extracellular vesicles (EVs) regulate intercellular communication by transporting intracellular cargo to recipient cells thereby altering the function of recipient cells. This study aimed to evaluate whether adipocyte‐derived EVs can act on hypothalamic neurons to modulate energy intake and to identify the EV‐associated non‐coding RNAs.

    更新日期:2019-11-18
  • Loss of nuclear ARC contributes to the development of cardiac hypertrophy in rats
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-27
    Fang Xie, Zhu‐Song Mei, Xue Wang, Tao Zhang, Yun Zhao, Shi‐Da Wang, Ling‐Jia Qian

    Cardiac hypertrophy and myocardial apoptosis are two major factors in heart failure. As a classical regulator of apoptosis, apoptosis repressor with caspase recruitment domain (ARC) has recently also been found to have a protective effect against hypertrophy. However, the mechanism underlying this effect is still not fully understood.

    更新日期:2019-11-18
  • Complex neural representation of odour information in the olfactory bulb
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-02
    Anan Li, Xiaoping Rao, Yang Zhou, Diego Restrepo

    The most important task of the olfactory system is to generate a precise representation of odour information under different brain and behavioural states. As the first processing stage in the olfactory system and a crucial hub, the olfactory bulb plays a key role in the neural representation of odours, encoding odour identity, intensity and timing. Although the neural circuits and coding strategies used by the olfactory bulb for odour representation were initially identified in anaesthetized animals, a large number of recent studies focused on neural representation of odorants in the olfactory bulb in awake behaving animals. In this review, we discuss these recent findings, covering (a) the neural circuits for odour representation both within the olfactory bulb and the functional connections between the olfactory bulb and the higher order processing centres; (b) how related factors such as sniffing affect and shape the representation; (c) how the representation changes under different states; and (d) recent progress on the processing of temporal aspects of odour presentation in awake, behaving rodents. We highlight discussion of the current views and emerging proposals on the neural representation of odorants in the olfactory bulb.

    更新日期:2019-11-18
  • Claudin‐15 forms a water channel through the tight junction with distinct function compared to claudin‐2
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-08
    Rita Rosenthal, Dorothee Günzel, Jörg Piontek, Susanne M. Krug, Carlos Ayala‐Torres, Caroline Hempel, Dian Theune, Michael Fromm

    Claudin‐15 is mainly expressed in the small intestine and indirectly involved in glucose absorption. Similar to claudin‐2 and ‐10b, claudin‐15 is known to form a paracellular channel for small cations. Claudin‐2, but not claudin‐10b, also forms water channels. Here we experimentally tested whether claudin‐15 also mediates water transport and if yes, whether water transport is Na+‐coupled, as seen for claudin‐2.

    更新日期:2019-11-18
  • Angiotensin II inhibits P‐glycoprotein in intestinal epithelial cells
    Acta Physiol. (IF 5.868) Pub Date : 2019-07-01
    Anoop Kumar, Shubha Priyamvada, Vikas Soni, Arivarasu N. Anbazhagan, Tarunmeet Gujral, Ravinder K. Gill, Waddah A. Alrefai, Pradeep K. Dudeja, Seema Saksena

    P‐glycoprotein (Pgp/MDR1) plays a major role in intestinal homeostasis. Decrease in Pgp function and expression has been implicated in the pathogenesis of IBD. However, inhibitory mechanisms involved in the decrease of Pgp in inflammation are not fully understood. Angiotensin II (Ang II), a peptide hormone predominantly expressed in the epithelial cells of the crypt‐villus junction of the intestine, has been shown to exert pro‐inflammatory effects in the gut. It is increased in IBD patients and animals with experimental colitis. Whether Ang II directly influences Pgp is not known.

    更新日期:2019-11-18
  • AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-21
    Peter M. Benz, Yindi Ding, Heike Stingl, Annemarieke E. Loot, Joana Zink, Ilka Wittig, Rüdiger Popp, Ingrid Fleming

    Protein kinase (PK) A anchoring protein (AKAP) 12 is a scaffolding protein that anchors PKA to compartmentalize cyclic AMP signalling. This study assessed the consequences of the downregulation or deletion of AKAP12 on endothelial cell migration and angiogenesis.

    更新日期:2019-11-18
  • Keeping heart homeostasis in check through the balance of iron metabolism
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-19
    Driton Vela

    Highly active cardiomyocytes need iron for their metabolic activity. In physiological conditions, iron turnover is a delicate process which is dependent on global iron supply and local autonomous regulatory mechanisms. Though less is known about the autonomous regulatory mechanisms, data suggest that these mechanisms can preserve cellular iron turnover even in the presence of systemic iron disturbance. Therefore, activity of local iron protein machinery and its relationship with global iron metabolism is important to understand cardiac iron metabolism in physiological conditions and in cardiac disease. Our knowledge in this respect has helped in designing therapeutic strategies for different cardiac diseases. This review is a synthesis of our current knowledge concerning the regulation of cardiac iron metabolism. In addition, different models of cardiac iron dysmetabolism will be discussed through the examples of heart failure (cardiomyocyte iron deficiency), myocardial infarction (acute changes in cardiac iron turnover), doxorubicin‐induced cardiotoxicity (cardiomyocyte iron overload in mitochondria), thalassaemia (cardiomyocyte cytosolic and mitochondrial iron overload) and Friedreich ataxia (asymmetric cytosolic/mitochondrial cardiac iron dysmetabolism). Finally, future perspectives will be discussed in order to resolve actual gaps in knowledge, which should be helpful in finding new treatment possibilities in different cardiac diseases.

    更新日期:2019-11-18
  • Muscle fibre activation and fatigue with low‐load blood flow restricted resistance exercise—An integrative physiology review
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-18
    Mathias Wernbom, Per Aagaard

    Blood flow‐restricted resistance exercise (BFRRE) has been shown to induce increases in muscle size and strength, and continues to generate interest from both clinical and basic research points of view. The low loads employed, typically 20%‐50% of the one repetition maximum, make BFRRE an attractive training modality for individuals who may not tolerate high musculoskeletal forces (eg, selected clinical patient groups such as frail old adults and patients recovering from sports injury) and/or for highly trained athletes who have reached a plateau in muscle mass and strength. It has been proposed that achieving a high degree of muscle fibre recruitment is important for inducing muscle hypertrophy with BFRRE, and the available evidence suggest that fatiguing low‐load exercise during ischemic conditions can recruit both slow (type I) and fast (type II) muscle fibres. Nevertheless, closer scrutiny reveals that type II fibre activation in BFRRE has to date largely been inferred using indirect methods such as electromyography and magnetic resonance spectroscopy, while only rarely addressed using more direct methods such as measurements of glycogen stores and phosphocreatine levels in muscle fibres. Hence, considerable uncertainity exists about the specific pattern of muscle fibre activation during BFRRE. Therefore, the purpose of this narrative review was (1) to summarize the evidence on muscle fibre recruitment during BFRRE as revealed by various methods employed for determining muscle fibre usage during exercise, and (2) to discuss reported findings in light of the specific advantages and limitations associated with these methods.

    更新日期:2019-11-18
  • Thyroid hormone regulation of neural stem cell fate: From development to ageing
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-17
    Jean‐David Gothié, Pieter Vancamp, Barbara Demeneix, Sylvie Remaud

    In the vertebrate brain, neural stem cells (NSCs) generate both neuronal and glial cells throughout life. However, their neuro‐ and gliogenic capacity changes as a function of the developmental context. Despite the growing body of evidence on the variety of intrinsic and extrinsic factors regulating NSC physiology, their precise cellular and molecular actions are not fully determined. Our review focuses on thyroid hormone (TH), a vital component for both development and adult brain function that regulates NSC biology at all stages. First, we review comparative data to analyse how TH modulates neuro‐ and gliogenesis during vertebrate brain development. Second, as the mammalian brain is the most studied, we highlight the molecular mechanisms underlying TH action in this context. Lastly, we explore how the interplay between TH signalling and cell metabolism governs both neurodevelopmental and adult neurogenesis. We conclude that, together, TH and cellular metabolism regulate optimal brain formation, maturation and function from early foetal life to adult in vertebrate species.

    更新日期:2019-11-18
  • O‐GlcNAcylation as a regulator of the functional and structural properties of the sarcomere in skeletal muscle: An update review
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-12
    Matthias Lambert, Charlotte Claeyssen, Bruno Bastide, Caroline Cieniewski‐Bernard

    Although the O‐GlcNAcylation process was discovered in 1984, its potential role in the physiology and physiopathology of skeletal muscle only emerged 20 years later. An increasing number of publications strongly support a key role of O‐GlcNAcylation in the modulation of important cellular processes which are essential for skeletal muscle functions. Indeed, over a thousand of O‐GlcNAcylated proteins have been identified within skeletal muscle since 2004, which belong to various classes of proteins, including sarcomeric proteins. In this review, we focused on these myofibrillar proteins, including contractile and structural proteins. Because of the modification of motor and regulatory proteins, the regulatory myosin light chain (MLC2) is related to several reports that support a key role of O‐GlcNAcylation in the fine modulation of calcium activation parameters of skeletal muscle fibres, depending on muscle phenotype and muscle work. In addition, another key function of O‐GlcNAcylation has recently emerged in the regulation of organization and reorganization of the sarcomere. Altogether, this data support a key role of O‐GlcNAcylation in the homeostasis of sarcomeric cytoskeleton, known to be disturbed in many related muscle disorders.

    更新日期:2019-11-18
  • To learn, to remember, to forget—How smart is the gut?
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-05
    Michael Schemann, Thomas Frieling, Paul Enck

    The enteric nervous system (ENS) resides within the gut wall and autonomously controls gut functions through coordinated activation of sensory, inter and motor neurons. Its activity is modulated by the enteric immune and endocrine system as well as by afferent and efferent nerves of the parasympathetic and sympathetic nervous system. The ENS is often referred to as the second brain and hence is able to perform sophisticated tasks. We review the evidence that the “smartness” of the ENS may even extend to its ability to learn and to memorize. Examples for habituation, sensitization, conditioned behaviour and long‐term facilitation are evidence for various forms of implicit learning. Moreover, we discuss how this may change not only basic Neurogastroenterology but also our understanding of development of gut diseases and chronic disorders in gut functions. At the same time, we identify open questions and future challenges to confirm learning, memory and memory deficits in the gut. Despite some remaining experimental challenges, we are convinced that the gut is able to learn and are tempted to answer the question with: Yes, the gut is smart.

    更新日期:2019-11-18
  • Chronic adult‐onset of growth hormone/IGF‐I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-02
    Juan Francisco Martín‐Rodríguez, Víctor Darío Ramos‐Herrero, Gloria G. Parras, Álvaro Flores‐Martínez, Ainara Madrazo‐Atutxa, David A. Cano, Agnès Gruart, José María Delgado‐García, Alfonso Leal‐Cerro, Rocío Leal‐Campanario

    Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin‐like growth factor I (IGF‐I), have been implicated in different brain functions, including neurogenesis. Long‐lasting elevated GH and IGF‐I levels result in non‐reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH‐secreting (GH‐S) GC cell line in rats leads to the controllable over‐secretion of GH and elevated IGF‐I levels, allowing the experimental study of their short‐term effects on brain functions.

    更新日期:2019-11-18
  • Oxygenation of adipose tissue: A human perspective
    Acta Physiol. (IF 5.868) Pub Date : 2019-06-02
    Ioannis G. Lempesis, Rens L. J. van Meijel, Konstantinos N. Manolopoulos, Gijs H. Goossens

    Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.

    更新日期:2019-11-18
  • The importance of being rhythmic: Living in harmony with your body clocks
    Acta Physiol. (IF 5.868) Pub Date : 2019-05-03
    Charna Dibner

    Circadian rhythms have developed in all light‐sensitive organisms, including humans, as a fundamental anticipatory mechanism that enables proactive adaptation to environmental changes. The circadian system is organized in a highly hierarchical manner, with clocks operative in most cells of the body ensuring the temporal coordination of physiological processes. Circadian misalignment, stemming from modern life style, draws increasing attention due to its tight association with the development of metabolic, cardiovascular, inflammatory and mental diseases as well as cancer. This review highlights recent findings emphasizing the role of the circadian system in the temporal orchestration of physiology, with a particular focus on implications of circadian misalignment in human pathologies.

    更新日期:2019-11-18
  • In search for better pharmacological prophylaxis for acute mountain sickness: looking in other directions
    Acta Physiol. (IF 5.868) Pub Date : 2015-03-09
    Hui Lu, Rong Wang, Juan Xiong, Hua Xie, Bengt Kayser, Zheng‐ping Jia

    Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia we suggest that directly or indirectly blunting specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that 1) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2) as low as 25 mmHg without AMS symptoms, 2) paradoxically AMS usually develops at much higher PaO2 levels, and 3) several biomarkers, suggesting initial activation of specific pathways at such PaO2, are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.

    更新日期:2019-11-18
  • Sprint exercise enhances skeletal muscle p70S6k phosphorylation and more so in females than in males
    Acta Physiol. (IF 5.868) Pub Date : 2011-12-26
    Mona Esbjörnsson, Håkan C Rundqvist, Henrik Mascher, Ted Österlund, O. Rooyackers, Eva Blomstrand, Eva Jansson

    Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross sectional area in females than males. Therefore, we tested the hypothesis that activation of mTOR signalling is more pronounced in females than in males. Healthy males (n=9) and females (n=8) performed three bouts of 30‐s sprint exercise with 20 min rest between.

    更新日期:2019-11-18
  • The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats
    Acta Physiol. (IF 5.868) Pub Date : 2010-08-17
    Fumiyo Matsuda, Harutoshi Sakakima, Yoshihiro Yoshida

    Aim: Exercise can be used to enhance neuroplasticity and facilitate motor recovery after a stroke in rats. We investigated whether treadmill running could reduce brain damage and enhance the expression of midkine (MK) and nerve growth factor (NGF), increase angiogenesis, and decrease the expression of caspase‐3.

    更新日期:2019-11-18
  • Effects of exercise training on adipogenesis of stromal‐vascular fraction cells in rat epididymal white adipose tissue
    Acta Physiol. (IF 5.868) Pub Date : 2010-06-28
    Takuya Sakurai, Satohiro Endo, Daisuke Hatano, Junetsu Ogasawara, Takako Kizaki, Shuji Oh‐ishi, Tetsuya Izawa, Hitoshi Ishida, Hideki Ohno

    Aim: Previous studies have shown that exercise training reduced white adipose tissue (WAT) mass compared to that in sedentary controls, and that the smaller mass contained fewer adipocytes. However, the effect of exercise training on adipogenesis is not completely clear. Therefore, we reexamined the effect of exercise training on adipocyte numbers in WAT and, if such an effect was found tested the adipogenic responses of stromal‐vascular fraction (SVF) cells containing adipose tissue‐derived stem cells (ADSC) in epididymal WAT from exercise‐trained (TR) rats.

    更新日期:2019-11-18
  • Mitochondrial Ca in heart failure with preserved ejection fraction – friend or foe?
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-15
    F. Hohendanner, D. Bode

    In this issue of Acta Physiologica Miranda‐Silva and Wüst et al. 1 explore mitochondrial and cytosolic Calcium (Ca) dynamics during excitation‐contraction coupling in a metabolic syndrome based model of heart failure with preserved ejection fraction (HFpEF).

    更新日期:2019-11-15
  • Evolutionary and cardio‐respiratory physiology of air‐breathing and amphibious fishes
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-13
    Christian Damsgaard, Vikram B. Baliga, Eric Bates, Warren Burggren, David J. McKenzie, Edwin Taylor, Patricia A. Wright

    Air‐breathing and amphibious fishes are essential study organisms to shed insight into the required physiological shifts that supported the full transition from aquatic water‐breathing fishes to terrestrial air‐breathing tetrapods. While the origin of air‐breathing in the evolutionary history of the tetrapods has received considerable focus, much less is known about the evolutionary physiology of air‐breathing among fishes. This review summarizes recent advances within the field with specific emphasis on the cardiorespiratory regulation associated with air‐breathing and terrestrial excursions, and how respiratory physiology of these living transitional forms are affected by development and personality. Finally, we provide a detailed and re‐evaluated model of the evolution of air‐breathing among fishes that serves as a framework for addressing new questions on the cardiorespiratory changes associated with it. This review highlights the importance of combining detailed studies on piscine air‐breathing model species with comparative multi‐species studies, to add an additional dimension to our understanding of the evolutionary physiology of air‐breathing in vertebrates.

    更新日期:2019-11-13
  • Adipocyte‐derived extracellular vesicles as new communication signals in the regulation of food intake
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-12
    Shivaprakash Jagalur Mutt, Karl‐Heinz Herzig

    Mechanisms of cross organ communication is vital for our bodies to maintain homeostasis. Secreted peptides, proteins and the autonomic nervous system have been the major regulators in metabolic adaptation. During the last decade significant scientific evidence has accumulated that extracellular vesicles (EVs), secreted by all cells, are involved cellular signaling [1, 2]. The EVs consists of different types, e.g. exosomes from the endosomal pathway, microvesicles from the cell surface and apoptotic bodies. They are 30‐2000 nm in size, loaded with proteins, lipids or nucleic acids and have a wide range of actions/functions in tissue repair, immunity, cardiometabolic diseases and carcinogenesis [3]. Pathological roles have also been recently described in insulin resistance [4, 5]. EVs are able to interact with the target cells via special receptors (e.g. integrins, proteoglycans), or internalized via phagocytosis or membrane fusion.

    更新日期:2019-11-13
  • Recent Advances in Blood Pressure Research
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-12
    Ralf Mrowka

    According to the World health organization (WHO) elevated blood pressure, known as arterial Hypertension, is a condition in which the arterial blood vessels have persistently raised pressure, putting them under increased stress. The higher the blood pressure, the higher the risk of damage to the heart and blood vessels in major organs such as the brain and kidneys. Hypertension is the most important preventable cause of heart disease and stroke worldwide.

    更新日期:2019-11-13
  • Nestin affects fusion pore dynamics in mouse astrocytes
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-07
    Eva Lasič, Saša Trkov Bobnar, Ulrika Wilhelmsson, Yolanda de Pablo, Milos Pekny, Robert Zorec, Matjaž Stenovec

    Astrocytes play a homeostatic role in the central nervous system and influence numerous aspects of neurophysiology via intracellular trafficking of vesicles. Intermediate filaments (IFs), also known as nanofilaments, regulate a number of cellular processes including organelle trafficking and adult hippocampal neurogenesis. We have recently demonstrated that the IF protein nestin, a marker of neural stem cells and immature and reactive astrocytes, is also expressed in some astrocytes in the unchallenged hippocampus and regulates neurogenesis through Notch signalling from astrocytes to neural stem cells, possibly via altered trafficking of vesicles containing the Notch ligand Jagged‐1.

    更新日期:2019-11-08
  • LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-06
    Xue‐Feng Pang, Xue Lin, Jian‐Jun Du, Ding‐Yin Zeng

    Dilated cardiomyopathy (DCM) is characterised by left ventricular dilation and associated with systolic dysfunction. Recent evidence has reported the high expression of latent transforming growth factor beta binding protein 2 (LTBP2) in heart diseases, which may play a role in regulating multiple biological functions of myocardial cells. Thus, this study set out to investigate the molecular mechanism and effects of LTBP2 in myocardial oxidative stress injury, fibrosis and remodelling in a rat model of DCM, with the involvement of NF‐κB signalling pathway.

    更新日期:2019-11-07
  • The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-06
    Thawatchai Khuanjing, Siripong Palee, Siriporn C. Chattipakorn, Nipon Chattipakorn

    Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.

    更新日期:2019-11-06
  • PGC‐1α plays a pivotal role in simvastatin‐induced exercise impairment in mice
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-04
    Miljenko Valentin Panajatovic, François Singh, Noëmi Johanna Roos, Urs Duthaler, Christoph Handschin, Stephan Krähenbühl, Jamal Bouitbir

    Statins decrease cardiovascular complications, but can induce myopathy. Here, we explored the implication of PGC‐1α in statin‐associated myotoxicity.

    更新日期:2019-11-04
  • Loss of CD36 protects against diet‐induced obesity but results in impaired muscle stem cell function, delayed muscle regeneration and hepatic steatosis
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-01
    Sandrine Verpoorten, Peggy Sfyri, David Scully, Robert Mitchell, Anastasia Tzimou, Vassilis Mougios, Ketan Patel, Antonios Matsakas

    The prevalence of obesity is a major risk factor for cardiovascular and metabolic diseases including impaired skeletal muscle regeneration. Since skeletal muscle regenerative capacity is regulated by satellite cells, we aimed to investigate whether a high‐fat diet impairs satellite cell function and whether this is linked to fatty acid uptake via CD36. We also aimed to determine whether loss of CD36 impacts on muscle redox homeostasis and skeletal muscle regenerative capacity.

    更新日期:2019-11-04
  • Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus
    Acta Physiol. (IF 5.868) Pub Date : 2019-11-01
    Clarissa M. D. Mota, Luiz G. S. Branco, Shaun F. Morrison, Christopher J. Madden

    Serotonin (5‐hydroxytryptamine, 5‐HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5‐HT.

    更新日期:2019-11-01
  • Doxorubicin‐induced skeletal muscle atrophy: Elucidating the underlying molecular pathways
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-31
    Anouk E. Hiensch, Kate A. Bolam, Sara Mijwel, Jeroen A. L. Jeneson, Alwin D. R. Huitema, Onno Kranenburg, Elsken van der Wall, Helene Rundqvist, Yvönne Wengstrom, Anne M. May

    Loss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta‐analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin‐induced muscle atrophy in both human and animal models.

    更新日期:2019-11-01
  • The sympathetic nervous system in acute kidney injury
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-31
    Olaf Grisk

    Acute kidney injury (AKI) is frequently accompanied by activation of the sympathetic nervous system (SNS). This may result from pre‐exisiting chronic diseases associated with sympathetic activation prior to AKI or it may be induced by stressors that ultimately lead to AKI such as endotoxins and arterial hypotension in circulatory shock. Conversely, sympathetic activation may also result from acute renal injury. Focusing on studies in experimental renal ischaemia and reperfusion (IR), this review summarizes the current knowledge on how the SNS is activated in IR‐induced AKI and on the consequences of sympathetic activation for the development of acute renal damage. Experimental studies show beneficial effects of sympathoinhibitory interventions on renal structure and function in response to IR. However, few clinical trials obtained in scenarios that correspond to experimental IR, namely major elective surgery, showed that peri‐operative treatment with centrally acting sympatholytics reduced the incidence of AKI. Apparently, discrepant findings on how sympathetic activation influences renal responses to acute IR‐induced injury are discussed and future areas of research in this field are identified.

    更新日期:2019-11-01
  • Syndecan‐4, a model proteoglycan to study endothelial glycocalyx mechanosensing and signal transduction
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-30
    Bernard M. van den Berg

    In the present issue of Acta Physiologica, Jiang, et al.1 tested how the endothelial glycocalyx transmits the blood flow shear stress to the cytoskeleton. In a series of large‐scale molecular dynamics computational experiments the dynamics of the proteoglycan syndecan‐4 force transmission is examined under varying conditions, i.e. blood flow velocity changes and proteoglycan sugar chain shedding.

    更新日期:2019-10-30
  • Nestin regulates vesicular dynamics in proliferative reactive astrocyte
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-23
    Jernej Jorgačevski, Alexei Verkhratsky

    In the present issue of Acta Physiologica the team of researchers lead by Robert Zorec and Milos Pekny [1] examined the role of nesting (the intermediate filament associated with proliferation and stem cell capacity) in the regulation of vesicular trafficking in reactive astrocytes in vitro. Reactive astrogliosis is a complex of biochemical, morphological and functional metamorphoses of astrocytes in response to pathological insults to the brain and to the spinal cord. Instigation of astrogliosis by various pathology‐related factors (generalised as damage‐associated and pathogen‐associated molecular patterns, DAMPs and PAMPs) produces multiple reactive phenotypes specific for the disease and context [2,3]. Conceptually, astrogliosis is a defensive response of astroglia; in certain conditions (for example in response to chronic or severe stress) it may turn maladaptive and generate neurotoxic astrocytes.

    更新日期:2019-10-24
  • Motor unit function during cold induced thermogenesis in muscle – new perspectives on old concepts
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-22
    Esa Hohtola, José González‐Alonso

    Endothermic animals are able to maintain a stable body core temperature in the cold by increasing active thermogenesis. While brown fat thermogenesis has recently received extensive attention, shivering (sensu lato = heat emanating from contraction of motor units as a response to cold), is the only common mechanism of adaptive thermogenesis to all endotherms, i.e. mammals and birds.

    更新日期:2019-10-23
  • Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-19
    Malek Kammoun, Jerome Piquereau, Lydie Nadal‐Desbarats, Sandra Même, Maud Beuvin, Gisèle Bonne, Vladimir Veksler, Yann Le Fur, Philippe Pouletaut, William Même, Frederic Szeremeta, Jean‐Marc Constans, Elizabeth S. Bruinsma, Molly H. Nelson Holte, Zeynab Najafova, Steven A. Johnsen, Malayannan Subramaniam, John R. Hawse, Sabine F. Bensamoun

    Tieg1 is involved in multiple signalling pathways, human diseases, and is highly expressed in muscle where its functions are poorly understood.

    更新日期:2019-10-21
  • Letter to the editor
    Acta Physiol. (IF 5.868) Pub Date : 2019-10-21
    Peter H. Sandal, Morten Damgaard, Niels H. Secher

    In April 2018, Acta Physiologica published a review entitled: ‘Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure’1. On the basis of data from 114 references including 47 species of mammals, Poulsen et al. 20181 investigated whether mean arterial pressure (MAP) scales to body mass (BM) and examined the effect of physiological and methodological confounders such as use of anaesthetics and restraint and choice of method for determination of blood pressure. We wish to contribute to these findings, by investigating to what extent BM and the vertical distance between the heart and brain contribute to MAP. Physiological variables that encompass a length or a time dimension scale to the size of the animal.

    更新日期:2019-10-21
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