1. Apocynin protects endothelial cells from endoplasmic reticulum stress-induced apoptosis via IRE1α engagement
- Author
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Weijin Zhang, Jie Wu, Guang-Ting He, Peixin Li, Xiaohui Liu, Qiaobing Huang, Xiaohua Guo, Lili Wu, and Zhongqing Chen
- Subjects
X-Box Binding Protein 1 ,inorganic chemicals ,0301 basic medicine ,XBP1 ,RNA Splicing ,Clinical Biochemistry ,Apoptosis ,Caspase 3 ,Protein Serine-Threonine Kinases ,Apocynin ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Endothelial cell ,Endoribonucleases ,Human Umbilical Vein Endothelial Cells ,Humans ,Molecular Biology ,NADPH oxidase ,biology ,Chemistry ,Endoplasmic reticulum ,Acetophenones ,IRE1α ,Cell Biology ,General Medicine ,Endoplasmic Reticulum Stress ,Cell biology ,Endothelial stem cell ,030104 developmental biology ,cardiovascular system ,Unfolded protein response ,biology.protein ,circulatory and respiratory physiology - Abstract
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 1α (IRE1α). Importantly, apocynin upregulated IRE1α 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 IRE1α involvement. These findings may provide a novel mechanistic explanation for the anti-apoptotic effect of apocynin in ER stress.
- Published
- 2018