HSP90 attenuates heat stress-induced myocardial injury in broilers via regulating the endoplasmic reticulum stress-protective autophagy pathway to inhibit apoptosis

Abstract

Global warming increases the risk of heart failure and sudden death in humans and animals due to heat stress (HS). HSP90 is important in maintaining protein structure and regulating ER homeostasis during HS. However, the exact mechanism of HS-induced myocardial injury and the specific regulatory role of HSP90 remain largely unclear. Therefore, we established the HS model using broilers and chicken primary myocardial cells (CPMCs) sensitive to HS and intervened with the ERS activator (tunicamycin, TM) or inhibitor (4-Phenylbutyric acid, 4-PBA), and the autophagy activator (Rapamycin) or antagonist (3-MA). The results showed that HS caused abnormal cardiac morphology and structure in broilers. Mechanistically, ERS, autophagy, and apoptosis were significantly promoted by HS in both the myocardial tissue and cardiomyocytes. However, intervention with TM or 4-PBA significantly exacerbated or reversed these changes, while Rapamycin or 3-MA alleviated or promoted apoptosis. Moreover, HSP90 directly regulates ERS by interacting with IRE1α or PERK. HSP90 knockdown enhances ERS-mediated autophagy and apoptosis, while HSP90 overexpression reverses these effects. In conclusion, the present research suggested that HS triggers ERS-mediated protective autophagy in broiler cardiomyocytes, which is beneficial for inhibiting apoptosis. Activating HSP90 may be a promising strategy to ameliorate HS-induced cardiac injury.

Keywords: Autophagy; Endoplasmic reticulum dependent apoptosis; HSP90.