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

Anwarul A. Akhand, Khaled Hossain, Masashi Kato, Toshio Miyata, Jun Du, Haruhiko Suzuki, Kiyoshi Kurokawa, Izumi Nakashima

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1228-1235
Number of pages8
JournalFree Radical Biology and Medicine
Issue number10
Publication statusPublished - 2001 Nov 15


  • ERK
  • Free radicals
  • Glyoxal
  • Methylglyoxal
  • MKP-1


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