Glyoxal and methylglyoxal induce aggregation and inactivation of ERK in human endothelial cells

被引:35
作者
Akhand, AA
Hossain, K
Kato, M
Miyata, T
Du, J
Suzuki, H
Kurokawa, K
Nakashima, I
机构
[1] Nagoya Univ, Grad Sch Med, Dept Immunol, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan
关键词
HUVEC; glyoxal; methylglyoxal; ERK; MKP-1; free radicals;
D O I
10.1016/S0891-5849(01)00702-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Increased production of glyoxal (GO) and methylglyoxal. (MGO) under oxidative stress is harmful to the cells. In this study, we examined the early signaling effect of GO/MGO on cultured human umbilical vein endothelial cells. Both GO and MGO induced tyrosine phosphorylation and aggregation of a number of cellular proteins. Aggregation occurred mainly for cell surface proteins such as Flk-1 and VE-cadherin, but barely for the majority of intracellular proteins. Interestingly, however, GO/MGO caused both aggregation and dephosphorylation of intracellular phospho-ERK for inactivation. This phospho-ERK dephosphorylation was mediated by orthovanadate-sensitive phosphatase activity accompanying chemical recruitment of MKP-1 to the aggregated phospho-ERK. Evidence was provided that GO/MGO upregulated MKP-1 activity that in turn dephosphorylated possibly co-aggregated phospho-ERK efficiently for inactivation. These results together suggest that GO and MGO trigger a novel pathway for chemical reaction-mediated downregulation of ERK. (C) 2001 Elsevier Science Inc.
引用
收藏
页码:1228 / 1235
页数:8
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