Vascular smooth muscle (VSM) cell migration is a critical step in the development of a neointima after angioplasty. Matrix metalloproteinases (MMPs) degrade the basement membrane and extracellular matrix, facilitating VSM cell migration. Recently, we demonstrated that nitric oxide (NO) inhibits interleukin-1 beta (IL-1 beta)-stimulated MMP-9 induction in rat aortic VSM cells. In this study, we examined the hypothesis that NO inhibits MMP-9 induction by attenuating superoxide generation and extracellular signal-regulated kinase (ERK) activation. Stimulation of VSM cells with IL-1 beta significantly (P<0.05) increased superoxide production, ERK activation, and MMP-9 induction. Pretreatment of VSM cells with the NO donor DETA NONOate significantly (P<0.05) decreased IL-1 beta -stimulated superoxide generation. In addition, pretreatment of VSM cells with a specific ERK pathway inhibitor, PD-98059, or DETA NONOate inhibited IL-1 beta -stimulated ERK activation and MMP-9 induction. Direct exposure of VSM cells to increased superoxide levels by treatment with xanthine/xanthine oxidase increased ERK activation and MMP-9 induction, whereas pretreatment of cells with PD-98059 significantly (P<0.05) inhibited xanthine/xanthine oxidase-stimulated ERK activation and MMP-9 induction. We conclude that NO inhibits IL-1<beta>-stimulated MMP-9 induction by inhibiting superoxide generation and subsequent ERK activation.
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Chamberlain, J
Gunn, J
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Gunn, J
Francis, S
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Francis, S
Holt, C
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Holt, C
Crossman, D
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Chamberlain, J
Gunn, J
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Gunn, J
Francis, S
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Francis, S
Holt, C
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h-index: 0
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England
Holt, C
Crossman, D
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Div Clin Sci,Sect Med,NGH, Sheffield S5 7AU, S Yorkshire, England