Apocynin protects endothelial cells from endoplasmic reticulum stress-induced apoptosis via IRE1α engagement

Endoplasmic reticulum (ER) stress-induced endothelial cell (EC) apoptosis has been implicated in a variety of human diseases. In addition to being regarded as an NADPH oxidase (NOX) inhibitor, apocynin (APO) exhibits an anti-apoptotic effect in various cells. The present study aimed to identify the protective role of apocynin in ER stress-mediated EC apoptosis and the underlying mechanisms. We found that ER stress resulted in a significant increase in c-Jun N-terminal kinase phosphorylation, and elicited caspase 3 cleavage and apoptosis. However, apocynin obviously attenuated EC apoptosis and this effect was partly dependent on ER stress sensor inositol-requiring enzyme 1 alpha (IRE1 alpha). Importantly, apocynin upregulated IRE1 alpha expression in both protein and mRNA levels and promoted the pro-survival XBP1 splicing. Our results suggest that apocynin protects ECs against ER stress-induced apoptosis via IRE1 alpha involvement. These findings may provide a novel mechanistic explanation for the anti-apoptotic effect of apocynin in ER stress.