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MitoTEMPO provides an antiarrhythmic effect in aged-rats through attenuation of mitochondrial reactive oxygen species.
Experimental Gerontology ( IF 3.3 ) Pub Date : 2020-04-20 , DOI: 10.1016/j.exger.2020.110961
Yusuf Olgar 1 , Deniz Billur 2 , Erkan Tuncay 1 , Belma Turan 1
Affiliation  

The death prevalence from cardiovascular disease is significantly high in elderly-populations, while mitochondrial-aging plays an important in abnormal function of vital organs through high mitochondrial ROS production. Mitochondria have a unique mode of action by providing ATP production and modulating the cytosolic Ca2+-signaling and maintain the redox status of cardiomyocytes. There is an aging-associated impairment in oxidative phosphorylation which causes a marked dysregulation of mitochondrial biogenesis. Therefore, we aimed to examine whether a mitochondria-targeting antioxidant, MitoTEMPO, can directly provide a cardioprotective effect on ventricular cardiomyocyte function under in vitro conditions. The MitoTEMPO-treatment (0.1 μM for 4-h) of aged-ventricular cardiomyocytes (from 24-mo-old rats), compared to those of the adults (from 8-mo-old rats) markedly augmented not only the depressed biochemical parameters but also the ultrastructure of mitochondria. It also provided marked protective action against increased mitochondrial superoxide formation and Bnip3 overexpression, which both markedly induce depolarized mitochondrial potential, increase reactive oxygen species, mitochondrial swelling and fission, and accelerate mitochondrial turnover via autophagy. Furthermore, it provided marked protection against spontaneous action potentials, via shortening the prolonged action potential duration, at most, through recovery in depressed K+-channel currents. Moreover, we determined significant recovery in the depressed intracellular Ca2+-changes under electrical stimulation in MitoTEMPO-treated the aged-cardiomyocytes. Overall, we provided important information associated with an antiarrhythmic action, thereby controlling cytosolic and mitochondrial Ca2+-handling, implying its possible protective role of mitochondria-targeting antioxidant-treatment during aging.

中文翻译:

MitoTEMPO通过降低线粒体活性氧的含量,在衰老大鼠中提供抗心律失常作用。

在老年人群中,心血管疾病的死亡患病率非常高,而线粒体衰老在通过高线粒体ROS产生对重要器官的异常功能中起着重要作用。线粒体具有独特的作用方式,可提供ATP产生并调节胞质Ca2 +信号传导,并维持心肌细胞的氧化还原状态。氧化磷酸化存在与衰老相关的损伤,这会导致线粒体生物发生的明显失调。因此,我们旨在研究在体外条件下靶向线粒体的抗氧化剂MitoTEMPO是否可以直接对心室心肌细胞功能提供心脏保护作用。老年心室心肌细胞(来自24个月大的大鼠)的MitoTEMPO处理(0.1μM,持续4小时),与成年动物(8岁以上的老鼠)相比,不仅显着增强了抑郁的生化参数,而且显着增强了线粒体的超微结构。它还提供了针对线粒体超氧化物形成增加和Bnip3过表达的显着保护作用,它们均能明显诱导线粒体去极化电位,增加活性氧,线粒体肿胀和裂变,并通过自噬促进线粒体更新。此外,通过缩短延长的动作电位持续时间,至多通过降低K +通道电流的恢复,它提供了针对自发动作电位的显着保护。此外,我们确定了在MitoTEMPO处理的老年心肌细胞的电刺激下,抑制的细胞内Ca2 +变化的显着恢复。总体,
更新日期:2020-04-22
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