Glyoxal and methylglyoxal induce lyoxal and methyglyoxal induce aggregation and inactivation of ERK in human endothelial cells.
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.
Akhand
A A
AA
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hossain
K
K
Kato
M
M
Miyata
T
T
Du
J
J
Suzuki
H
H
Kurokawa
K
K
Nakashima
I
I
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
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