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 [1 ]
Siow, YL [1 ]
O, K [1 ]
机构
[1] Univ Hong Kong, Fac Med, Inst Cardiovasc Sci & Med, Dept Pharmacol, Pokfulam, Hong Kong, Peoples R China
关键词
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.
引用
收藏
页码:817 / 825
页数:9
相关论文
共 52 条
  • [1] The NF-kappa B and I kappa B proteins: New discoveries and insights
    Baldwin, AS
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 : 649 - 683
  • [2] Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion
    Brand, K
    Page, S
    Rogler, G
    Bartsch, A
    Brandl, R
    Knuechel, R
    Page, M
    Kaltschmidt, C
    Baeuerle, PA
    Neumeier, D
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (07) : 1715 - 1722
  • [3] Role of nuclear factor-kappa B in atherogenesis
    Brand, K
    Page, S
    Walli, AK
    Neumeier, D
    Baeuerle, PA
    [J]. EXPERIMENTAL PHYSIOLOGY, 1997, 82 (02) : 297 - 304
  • [4] BROWN Z, 1994, AM J PATHOL, V145, P913
  • [5] Site-specific phosphorylation of I kappa B alpha by a novel ubiquitination-dependent protein kinase activity
    Chen, ZJ
    Parent, L
    Maniatis, T
    [J]. CELL, 1996, 84 (06) : 853 - 862
  • [6] HYPERHOMOCYSTEINEMIA - AN INDEPENDENT RISK FACTOR FOR VASCULAR-DISEASE
    CLARKE, R
    DALY, L
    ROBINSON, K
    NAUGHTEN, E
    CAHALANE, S
    FOWLER, B
    GRAHAM, I
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (17) : 1149 - 1155
  • [7] Very low-density lipoprotein activates nuclear factor-κB in endothelial cells
    Dichtl, W
    Nilsson, L
    Goncalves, I
    Ares, MPS
    Banfi, C
    Calara, F
    Hamsten, A
    Eriksson, P
    Nilsson, J
    [J]. CIRCULATION RESEARCH, 1999, 84 (09) : 1085 - 1094
  • [8] Homocyst(e)ine: An important risk factor for atherosclerotic vascular disease
    Duell, PB
    Malinow, MR
    [J]. CURRENT OPINION IN LIPIDOLOGY, 1997, 8 (01) : 28 - 34
  • [9] Calcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-κB in primary human vascular smooth muscle cells
    Eickelberg, O
    Roth, M
    Mussmann, R
    Rüdiger, JJ
    Tamm, M
    Perruchoud, AP
    Block, LH
    [J]. CIRCULATION, 1999, 99 (17) : 2276 - 2282
  • [10] Nuclear factor-κB regulates induction of apoptosis and inhibitor of apoptosis protein-1 expression in vascular smooth muscle cells
    Erl, W
    Hansson, GK
    de Martin, R
    Draude, G
    Weber, KSC
    Weber, C
    [J]. CIRCULATION RESEARCH, 1999, 84 (06) : 668 - 677