Background and purpose: The activation of endoplasmic reticulum(ER) stress by type 2 diabetes leads to the folding dysfunction of glucagon-like peptide-1 receptor(GLP-1R), which often results in the local reduction of vascular protective nitric oxide(NO) by endothelial cells. This study investigated the protective role of stress-associated endoplasmic reticulum protein 1(SERP1) against diabetes mellitus(DM) relevant vascular complications.
Experimental approach: Rat aortic endothelial cells (RAOECs) were exposed to high glucose (HG) to induce ER stress on endothelial cells. Adenosine 5‘-monophosphate -activated protein kinase(AMPK) and endothelial nitric oxide synthase (eNOS) phosphorylation and ER stress responsive protein G-protein coupled receptor 78(GPR78) were determined by western blotting.The interaction between SERP1 and GLP-1R was confirmed by co-immunoprecipitation(co-IP). NO release in endothelial cells was measured by Nitric Oxide Colorimetric Assay Kit.
Key results: HG could induce ER stress therefore upregulated the expression of ER stress responsive protein GPR78 shown by western blot annalysis. Overexpression of SERP1 in endothelial cells by pcMV6-SERP1 significantly decreased the expresssion of GPR78 and increased the release of liraglutide induced NO according with the increasement of AMPK and eNOS phosphorylations against ER stress. More importantly, western blotting showed that ,the molecular weight of GLP-1R increased more significantly in the SERP1 overexpression group compared with vector control group, which suggests that SERP1 plays a role in the process during GLP-1R post-transcriptional modification.
Conclusions and implications: Our data suggest SERP1 can be a novel protective protein in perventing diabetic vascular complications by improving endothelial cells’ capacity for generating nitric oxide against DM relevant ER stress.
Posted by: Lishuai Feng, China (02-Dec-2016)