Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK Pathway.

International Journal of Molecular Sciences
Sujin KimChang-Hoon Woo

Abstract

It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction than glucose itself. Recent reports showed that high glucose and MGO induced endoplasmic reticulum (ER) stress and myocyte apoptosis in ischemic heart disease was inhibited by apelin. The goal of the study is to investigate the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress in endothelial cells, and to examine whether apelin-13, a cytoprotective polypeptide ligand, protects MGO-induced aortic endothelial dysfunction. MGO-induced ER stress and apoptosis were determined by immunoblotting and MTT assay in HUVECs. Aortic endothelial dysfunction was addressed by en face immunostaining and acetylcholine-induced vasodilation analysis with aortic rings from mice treated with MGO in the presence or absence of apelin ex vivo. TUDCA, an inhibitor of ER stress, inhibited MGO-induced apoptosis and reduction of cell viability, suggesting that MGO signaling to endothelial apoptosis is mediated via ER stress, which leads to activation of unfolded protein responses (UPR). In addition, MGO-induced UPR and aortic endothelial dysfunction were significantly diminished by a...Continue Reading

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Citations

Mar 11, 2021·Free Radical Biology & Medicine·José-Luis García-GiménezFederico V Pallardó
Apr 27, 2021·Journal of Receptor and Signal Transduction Research·Mustafa Kırça, Akın Yeşilkaya
Jun 7, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Sushmita Bora, Prashant Shankarrao Adole
Jul 15, 2021·Molecular and Cellular Biochemistry·Shreya DasArunima Sengupta

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Methods Mentioned

BETA
protein folding
protein assay
flow cytometry

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis