Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway i
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ORIGINAL PAPER
Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway in rats 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 Received: 8 May 2020 / Revised: 29 October 2020 / Accepted: 3 November 2020 # Cell Stress Society International 2020
Abstract 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 heatstressed 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 stressinduced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress. Keywords Heat stress . Unfolded protein response . Soleus muscle . Gastrocnemius muscle . Oxidative stress . Apoptosis
Abbreviations HS Heat stress GS Gastrocnemius SL Soleus ER Endoplasmic reticulum UPR Unfolded protein response
* Pooja Chaudhary [email protected] 1
Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Timarpur, Delhi 110054, India
2
Department of Biochemistry, Panjab University, sector 25, Chandigarh, India
Introduction Every homoeothermic organism operates at a fixed temperature range known as the thermoneutral zone at which they can maintain an adequate balance between heat production and loss thereby attaining homeostasis (Swanlund et al. 2008). Exposure to high environmental temperature and strenuous physical activities can cause excessive gain
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