Expression of monocyte chemoattractant protein-1 by nonenzymatically glycated albumin (Amadori adducts) in vascular smooth muscle cells.
The biological effects of Amadori adducts that are early nonenzymatically glycated protein on vascular cells were poorly defined. We examined the effect of glycated serum albumin (GA) on the expression of monocyte chemoattractant protein-1(MCP-1) that is an important chemokine recruiting monocyte to blood vessel. GA increased MCP-1 mRNA expression with a peak after 3 h of stimulation. The induction of MCP-1 by GA was dose-dependent. The MCP-1 mRNA expression by GA was completely inhibited by PD98059 and genistein that inhibit mitogen activated protein (MAP) kinase kinase and tyrosine kinase, respectively. N-Acetylcysteine, a potent antioxidant, also suppressed the GA-induced MCP-1 expression. These results suggest that GA induces production of reactive oxygen species and activates tyrosine kinase and MAP kinase in VSMC. Activation of these signals results in MCP-1 expression. GA-induced MCP-1 expression may be one of the mechanisms by which the diabetic patients suffer from accelerated atherosclerosis.
Ichiki
T
T
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. ichiki@cardiol.med.kyushu-u.ac.jp
Funakoshi
Y
Y
Ito
K
K
Takeshita
A
A
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017127:Glycation End Products, Advanced; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014158:Transcription, Genetic; D000093423:Glycated Serum Albumin
D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000093423:Glycated Serum Albumin