Role of endoplasmic reticulum oxidase 1α in H9C2 cardiomyocytes following hypoxia/reoxygenation injury

Endoplasmic reticulum (ER) oxidase 1 alpha (ERO1 alpha) is a glycosylated flavoenzyme that is located on the luminal side of the ER membrane, which serves an important role in catalyzing the formation of protein disulfide bonds and ER redox homeostasis. However, the role of ERO1 alpha in myocardial hypoxia/reoxygenation (H/R) injury remains largely unknown. In the present study, ERO1 alpha expression levels in H9C2 cardiomyocytes increased following H/R, reaching their highest levels following 3 h of hypoxia and 6 h of reoxygenation. In addition, H/R induced apoptosis, and significantly increased expression levels of ER stress (ERS) markers 78 kDa glucose-regulated protein and C/EBP homologous protein. Moreover, the genetic knockdown of ERO1 alpha using short hairpin RNA suppressed cell apoptosis, caspase-3 activity, expression levels of cleaved caspase-12 and cytochrome c in the cytoplasm. Overall, this suggested that ERO1 alpha knockdown may protect against H/R injury. The ERS activator tunicamycin (TM) was used to counteract the ERO1 alpha -induced reduction in ERS; however, the percentage of apoptotic cells and the level of mitochondrial damage did not change. In conclusion, the results from the present study suggested that ERO1 alpha knockdown may protect H9C2 cardiomyocytes from H/R injury through inhibiting intracellular ROS production and increasing intracellular levels of Ca2+, suggesting that ERO1 alpha may serve an important role in H/R.