HSP70 protects H9C2 cells from hypoxia and reoxygenation injury through STIM1/IP3R

Abstract

Hypoxia/reoxygenation (H/R) is used as an in vivo model of ischemia/reperfusion injury, and myocardial ischemia can lead to heart disease. Calcium overload is an important factor in myocardial ischemia–reperfusion injury and can lead to apoptosis of myocardial cells. Therefore, it is of great clinical importance to find ways to regulate calcium overload and reduce apoptosis of myocardial cells, and thus alleviate myocardial ischemia–reperfusion injury. There is evidence that heat shock protein 70 (HSP70) has a protective effect on the myocardium, but the exact mechanism of this effect is not completely understood. Stromal interaction molecule 1 and inositol 1,4,5-triphosphate receptor (STIM/1IP3R) play an important role in myocardial ischemia–reperfusion injury. Therefore, this study aimed to investigate whether HSP70 plays an anti-apoptotic role in H9C2 cardiomyocytes by regulating the calcium overload pathway through STIM1/IP3R. Rat H9C2 cells were subjected to transient oxygen and glucose deprivation (incubated in glucose-free medium and hypoxia for 6 h) followed by re-exposure to glucose and reoxygenation (incubated in high glucose medium and reoxygenation for 4 h) to simulate myocardial ischemia reperfusion-induced cell injury. H9C2 cell viability was significantly decreased, and lactate dehydrogenase (LDH) release and apoptosis were significantly increased after oxygen and glucose deprivation. Transfection of HSP70 into H9C2 cells could reduce the corresponding effect, increase cell viability and anti-apoptotic signal pathway, and reduce the apoptotic rate and pro-apoptotic signal pathway. After hypoxia and reoxygenation, the expression of STIM1/IP3R and intracellular calcium concentration of HSP70-overexpressed H9C2 cells were significantly lower than those of hypoxia cells. Similarly, direct silencing of STIM1 by siRNA significantly increased cell viability and expression of anti-apoptotic protein Bcl-2 and decreased apoptosis rate and expression of pro-apoptotic protein BAX. These data are consistent with HSP70 overexpression. These results suggest that HSP70 abrogates intracellular calcium overload by inhibiting upregulation of STIM1/IP3R expression, thus reducing apoptosis in H9C2 cells and playing a protective role in cardiomyocytes.

Cebpd Regulates Oxidative Stress and Inflammatory Responses in Hypertensive Cardiac Remodeling

“…IP3R is a key regulator of SBP and contractility of VSMCs (53). Upregulation of IP3R is associated with hypoxia and reoxygenation-induced cardiomyocyte injury (54). According to our results, CEBPD enriched on the miR-96-5p promoter, and the binding relationships between CEBPD and miR-96-5p, miR-96-5p and IP3R were further verified by the dual-luciferase assay.…”

Transcriptomic responses of the liver of mandarin fish (Siniperca chuatsi) under hypoxic stress

“…Elevation of complement C3 in the liver of Eurasian perch, an important central component of the immune system, was induced by hypoxia, suggesting that the quantity and activity of complement system proteins are changed by a single hypoxia shock (Douxfils et al ., 2012). Recent studies (Liu et al ., 2022; Salnikow et al ., 2002; Zhang et al ., 2016) indicated that Ca 2+ was related to the cellular reaction of lower oxygen stress, and the free intracellular Ca 2+ of endothelial cells increased significantly after 2 h of hypoxia stress. Therefore, hypoxia can initiate many cascade reactions to help organisms adapt to lower oxygen conditions.…”