title: Glyoxal and methylglyoxal induce lyoxal and methyglyoxal induce aggregation and inactivation of ERK in human endothelial cells.
abstract: 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.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A A
authors.initials: AA
authors.lastname: Akhand
authors.forename: K
authors.initials: K
authors.lastname: Hossain
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: I
authors.initials: I
authors.lastname: Nakashima
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006037:Glyoxal / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D006037:Glyoxal; D011765:Pyruvaldehyde; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases