Methylglyoxal Triggers Human Aortic Endothelial Cell Dysfunction via Modulating KATP/MAPK pathway.

Methylglyoxal Triggers Human Aortic Endothelial Cell Dysfunction via Modulating KATP/MAPK pathway. Am J Physiol Cell Physiol. 2019 Apr 17;: Authors: Wang Y, Hall LM, Kujawa M, Li H, Zhang X, O'Meara M, Ichinose T, Wang JM Abstract Endothelial dysfunction is one of the key risk factors in diabetes-related multi-organ damage. Methylglyoxal (MGO), a highly reactive dicarbonyl mainly generated as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids and lipids, resulting in structural and functional changes of these targets and can form advanced glycation end products (AGEs). However, exactly how MGO causes endothelial cell dysfunction is not clear. Human aortic endothelial cells (HAECs) from healthy (H-HAECs) and type 2 diabetic (D-HAECs) donors were cultured in endothelial growth media (EGM-2). D-HAECs demonstrated impaired tube formation (on Matrigel) and proliferation (MTT assay), as well as increased apoptosis (TUNEL staining), compared with H-HAECs. H-HAECs were treated with MGO (10µM) for 24 hours with or without ATP-sensitive potassium channel (KATP) channel antagonist glibenclamide (1µM). MGO significantly impaired H-HAECs tube formation and proliferation and induced cell apoptosis which was reversed by glibenclamide. Meanwhile, activation of MAPK pathways p38 kinase, JNK, and ERK (determined by Western blot analyses of their phosphorylated forms...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research