title: Intracellular redox status modulates monocyte chemoattractant protein-1 expression stimulated by homocysteine in endothelial cells.
abstract: Homocystinemia has been identified as an independent risk factor for atherosclerosis. Monocyte chemoattractant protein-l (MCP-l) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The authors investigated the role of intracellular redox status in the expression of MCP-l stimulated by homocysteine in endothelial cells. Homocysteine stimulated MCP-1 mRNA expression and protein production in a time-dependent and dose-dependent manner in endothelial cells, decreased intracellular glutathione (GSH) and protein thiol levels, as well as G6PDH activity and NADPH levels. Thiol reduced reagents, GSH, and dithiothreitol levels, and reversed the MCP-l mRNA expression and protein production in endothelial cells; in addition, thiol oxidized reagent, diamide, and BSO levels, and markedly potentiated homocysteine-mediated up-regulation of MCP-l mRNA expression and protein production in endothelial cells. These results demonstrate that homocysteine can trigger overexpression of the MCP-1 gene by altering the intracellular redox status, suggesting that the homocysteine-induced changes in the intracellular redox status play an important role in modulating the expression of MCP-l in endothelial cells.
authors.affiliation: Institute of Biophysics, Academia Sinica, 15 Datun Road, Chaoyang District, Beijing 100101, P.R. China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Zhang
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Cao
authors.forename: Jing-Fen
authors.initials: JF
authors.lastname: Qin
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D018932:Chemokine CCL2; D006710:Homocysteine; D009249:NADP; D005978:Glutathione