Xiang Gu

Endoplasmic reticulum (ER) stress and autophagy are involved in myocardial ischemia‑reperfusion (I/R) injury; however, their roles in this type of injury remain unclear. The present study investigated the roles of ER stress and autophagy, and their underlying mechanisms, in H9c2 cells during hypoxia/reoxygenation (H/R) injury. Cell viability was detected by CCK‑8 assay. The autophagy flux was monitored with mCherry‑GFP‑LC3‑adenovirus transfection. The expression levels of autophagy‑related proteins and ER stress‑related proteins were measured by western blotting. Apoptosis was detected by flow cytometry and western blotting. The results indicated that autophagy was induced, ER stress was activated and apoptosis was promoted in H9c2 cells during H/R injury. The inhibition of ER stress by 4‑phenylbutyrate or C/EBP homologous protein (CHOP)‑targeting small interfering RNA (siRNA) decreased autophagy and ameliorated cell apoptosis during H/R injury. Activation of autophagy by rapamycin attenuated ER stress and ameliorated cell apoptosis. Inhibition of autophagy by 3‑methyladenine or Beclin1‑targeting siRNA aggravated ER stress and exacerbated cell apoptosis, and activation of ER stress by thapsigargin decreased autophagy and induced cell apoptosis. Collectively, the findings of the present study demonstrated that H/R induced apoptosis and autophagy via ER stress in H9c2 cells, and that CHOP may serve an important role in ER stress‑induced autophagy and apoptosis. Autophagy, as an adaptive response, was activated by ER stress and alleviated ER stress‑induced cell apoptosis during H/R injury.

Endoplasmic reticulum (ER) stress–induced apoptosis is a major cause of myocardial ischemia/reperfusion (I/R) injury. Emerging evidence indicates that glucagon-like peptide-1 (GLP-1) has potential cardioprotective effects. However, the precise mechanisms underlying the involvement of GLP-1 in I/R injury remain largely unknown. In the present study, we aimed to determine whether GLP-1 attenuates hypoxia/reoxygenation (H/R) injury in cardiomyocytes and to further elucidate the underlying signaling pathway. The results indicate that GLP-1 reversed the increased apoptotic ratio, the increased lactate dehydrogenase (LDH) levels, the reduced cell viability, the increased Caspase-3 activity, and the increased Bax/Bcl-2 ratio caused by H/R. Importantly, GLP-1 significantly decreased the expression of H/R-induced ER stress proteins (GRP78, CHOP) and Caspase-12. In addition, we found that GLP-1 increased the expression of p-Akt in H9c2 cells with H/R injuries, and that the protective action of GLP-1 against H/R-induced injury was blocked by the GLP-1 receptor (GLP-1R) inhibitor Exendin9-39 and the PI3K inhibitor LY294002. Exendin9-39 and LY294002 also blocked the downregulation of ER stress protein expression by GLP-1, after H/R injury. Therefore, we have shown that GLP-1 exerts its cardioprotective effects by alleviating ER stress–induced apoptosis due to H/R injury and that these effects are most likely associated with the activation of GLP-1R/PI3K/Akt signaling pathway.

A Protective Mechanism of Glucogon-like Peptide-1 on AGEs-Induced H9C2 Cardiomyocytes Injury through Inhibiting ROSAutophagy Pathway, Cardiology and Cardio