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 (0.05Ő0.2mM) 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 κB (NF-κB). Further investigation demonstrated that the activation of NF-κB was the result of a PKC-mediated reduction in the expression of inhibitory protein (IκBα) mRNA and protein in homocysteine-treated cells. Oxidative stress might also be involved in the activation of NF-κB 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-κB is responsible for homocysteine-induced MCP-1 expression in VSMCs. These results suggest that homocysteine-stimulated MCP-1 expression via NF-κB activation may play an important role in atherogenesis.
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December 2000
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Research Article|
December 08 2000
Homocysteine stimulates nuclear factor κB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C
Guoping WANG
;
Guoping WANG
1Department of Pharmacology, Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Pokfulam, Hong Kong, People's Republic of China
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Yaw L. SIOW
;
Yaw L. SIOW
1Department of Pharmacology, Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Pokfulam, Hong Kong, People's Republic of China
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Karmin O
Karmin O
1
1Department of Pharmacology, Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Pokfulam, Hong Kong, People's Republic of China
1To whom correspondence should be addressed (e-mail okarmin@hkucc.hku.hk).
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Biochem J (2000) 352 (3): 817–826.
Article history
Received:
February 10 2000
Revision Received:
September 11 2000
Accepted:
October 06 2000
Citation
Guoping WANG, Yaw L. SIOW, Karmin O; Homocysteine stimulates nuclear factor κB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C. Biochem J 15 December 2000; 352 (3): 817–826. doi: https://doi.org/10.1042/bj3520817
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