Homocysteine stimulates nuclear factor κB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells:: a possible role for protein kinase C
被引:112
作者:
Wang, GP
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机构:
Univ Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R ChinaUniv Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R China
Wang, GP
[1
]
Siow, YL
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机构:
Univ Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R ChinaUniv Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R China
Siow, YL
[1
]
O, K
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h-index: 0
机构:
Univ Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R ChinaUniv Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R China
O, K
[1
]
机构:
[1] Univ Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R China
atherosclerosis;
calcium;
I kappa B alpha;
oxidative stress;
phosphorylation;
D O I:
10.1042/0264-6021:3520817
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of arterial walls. Although many factors that induce MCP-1 expression have been identified, the effect of homocysteine on the expression of MCP-1 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of homocysteine in MCP-1 expression in human aorta vascular smooth-muscle cells (VSMCs). After VSMCs were incubated with homocysteine for various time periods, a nuclease protection assay and ELISA were performed. Homocysteine (0.05-0.2 mM) significantly increased the expression of MCP-1 mRNA (up to 2.7-fold) and protein (up to 3.3-fold) in these cells. The increase in MCP-1 expression was associated with the activation of protein kinase C (PKC) as well as nuclear factor kappaB (NF-kappaB). Further investigation demonstrated that the activation of NF-kappaB was the result of a PKC-mediated reduction in the expression of inhibitory protein (I kappaB alpha) mRNA and protein in homocysteine-treated cells. Oxidative stress might also be involved in the activation of NF-kappaB by homocysteine in VSMCs. In conclusion, the present study has clearly demonstrated that the activation of PKC as well as superoxide production followed by activation of NF-kappaB is responsible for homocysteine-induced MCP-1 expression in VSMCs. These results suggest that homocysteine-stimulated MCP-1 expression via NF-kappaB activation may play an important role in atherogenesis.