BMAL1 involved in autophagy and injury of thoracic aortic endothelial cells of rats induced by intermittent heat stress through the AMPK/mTOR/ULK1 pathway

Abstract

Physiological activities of the body exhibit an obvious biological rhythm. At the core of the circadian rhythm, BMAL1 is the only clock gene whose deletion leads to abnormal physiological functions. However, whether intermittent heat stress influences cardiovascular function by altering the circadian rhythm of clock genes has not been reported. This study aimed to investigate whether intermittent heat stress induces autophagy and apoptosis, and the effects of BMAL1 on thoracic aortic autophagy and apoptosis. An intermittent heat stress model was established in vitro, and western blotting and immunofluorescence were used to detect the expression of autophagy, apoptosis, the AMPK/mTOR/ULK1 pathway, and BMAL1. After BMAL1 silencing, RT-qPCR was performed to detect the expression levels of autophagy and apoptosis-related genes. Our results suggest that heat stress induces autophagy and apoptosis in RTAECs. In addition, intermittent heat stress increased the phosphorylation of AMPK and ULK1, but reduced the phosphorylation of mTOR, AMPK inhibitor Compound C reversed the phosphorylation of AMPK, mTOR, and ULK1, and Beclin1 and LC3-II/LC3-I were downregulated. Furthermore, BMAL1 expression was elevated in vitro and shBMAL1 decreased autophagy and apoptosis. We revealed that intermittent heat stress induces autophagy and apoptosis, and that BMAL1 may be involved in the occurrence of autophagy and apoptosis.

Keywords: Apoptosis; Autophagy; BMAL1; Intermittent heat stress; RTAEC.