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Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway in rats
Cell Stress and Chaperones ( IF 3.8 ) Pub Date : 2020-11-18 , DOI: 10.1007/s12192-020-01178-x
Shivani Sharma 1, 2 , Pooja Chaudhary 1 , Rajat Sandhir 2 , Abhishek Bharadwaj 1 , Rajinder K Gupta 1 , Rahul Khatri 1 , Amir Chand Bajaj 1 , T P Baburaj 1 , Sachin Kumar 1 , M S Pal 1 , Prasanna K Reddy 1 , Bhuvnesh Kumar 1
Affiliation  

The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.



中文翻译:

大鼠比目鱼肌和腓肠肌热诱导的内质网应激及对UPR通路的不同反应

本研究旨在研究氧化(比目鱼肌)和糖酵解(腓肠肌)肌肉对热诱导的内质网 (ER) 应激的不同反应。据推测,由于成分和功能的差异,两种肌肉对急性热应激的反应不同。为了解决这个问题,雄性 Sprague Dawley 大鼠(12/组)经受热中性(25°C)或热应激(42°C)条件 1 小时。去除比目鱼肌和腓肠肌用于暴露后分析。在热暴露后,在两种肌肉中都观察到体温和自由基的产生显着增加。这进一步导致热应激肌肉中蛋白质羰基含量、AOPP 和脂质过氧化显着增加。与腓肠肌相比,这些变化在热应激比目鱼肌中更为明显。未折叠、变性蛋白质的积累导致内质网应激,导致未折叠蛋白质反应 (UPR) 途径的激活。与腓肠肌相比,比目鱼肌 UPR 换能器的表达显着更高。在热应激的比目鱼肌中也观察到静息细胞内钙离子的显着升高。C/EBP 同源蛋白和 Caspase12 的显着上调表明,比目鱼肌中错误折叠蛋白的细胞超载激活了 ER 诱导的细胞凋亡。该研究提供了肌肉在热应激下对 UPR 的不同反应的详细机制表示。数据表明,比目鱼肌主要是一种氧化肌肉,更容易受到热应激诱导的损伤,表现为细胞凋亡增强。这项研究可能有助于制定缓解策略,以改善热应激下的肌肉表现。

更新日期:2020-11-19
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