Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells

被引:51
作者
Gurjar, MV [1 ]
DeLeon, J [1 ]
Sharma, RV [1 ]
Bhalla, RC [1 ]
机构
[1] Univ Iowa, Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA
关键词
reactive oxygen species; matrix metalloproteinases; extracellular signal-regulated kinase; vascular smooth muscle cells; interleukin-1; beta; nitric oxide;
D O I
10.1152/jappl.2001.91.3.1380
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:1380 / 1386
页数:7
相关论文
共 43 条
  • [1] DIFFERENTIAL ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES BY H2O2 AND O-2(-) IN VASCULAR SMOOTH-MUSCLE CELLS
    BAAS, AS
    BERK, BC
    [J]. CIRCULATION RESEARCH, 1995, 77 (01) : 29 - 36
  • [2] SMOOTH-MUSCLE CELL-MIGRATION AND MATRIX METALLOPROTEINASE EXPRESSION AFTER ARTERIAL INJURY IN THE RAT
    BENDECK, MP
    ZEMPO, N
    CLOWES, AW
    GALARDY, RE
    REIDY, MA
    [J]. CIRCULATION RESEARCH, 1994, 75 (03) : 539 - 545
  • [3] IL-1 beta stimulates superoxide and delayed peroxynitrite production by pulmonary vascular smooth muscle cells
    Boota, A
    Zar, H
    Kim, YM
    Johnson, B
    Pitt, B
    Davies, P
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1996, 271 (06) : L932 - L938
  • [4] Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells
    Brown, MR
    Miller, FJ
    Li, WG
    Ellingson, AN
    Mozena, JD
    Chatterjee, P
    Engelhardt, JF
    Zwacka, RM
    Oberley, LW
    Fang, X
    Spector, AA
    Weintraub, NL
    [J]. CIRCULATION RESEARCH, 1999, 85 (06) : 524 - 533
  • [5] Reduction-oxidation (redox) state regulation of matrix metalloproteinase activity in human fetal membranes
    Buhimschi, IA
    Kramer, WB
    Buhimschi, CS
    Thompson, LP
    Weiner, CP
    [J]. AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2000, 182 (02) : 458 - 464
  • [6] Endothelial dysfunction in cardiovascular diseases - The role of oxidant stress
    Cai, H
    Harrison, DG
    [J]. CIRCULATION RESEARCH, 2000, 87 (10) : 840 - 844
  • [7] Temporal and spatial distribution of interleukin-1β in balloon injured porcine coronary arteries
    Chamberlain, J
    Gunn, J
    Francis, S
    Holt, C
    Crossman, D
    [J]. CARDIOVASCULAR RESEARCH, 1999, 44 (01) : 156 - 165
  • [8] MATRIX METALLOPROTEINASES AND CARDIOVASCULAR-DISEASE
    DOLLERY, CM
    MCEWAN, JR
    HENNEY, AM
    [J]. CIRCULATION RESEARCH, 1995, 77 (05) : 863 - 868
  • [9] Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells
    Eberhardt, W
    Beeg, T
    Beck, KF
    Walpen, S
    Gauer, S
    Böhles, H
    Pfeilschifter, J
    [J]. KIDNEY INTERNATIONAL, 2000, 57 (01) : 59 - 69
  • [10] Enhanced recovery of injury-caused downregulation of paxillin protein by eNOS gene expression in rat carotid artery - Mechanism of NO inhibition of intimal hyperplasia?
    Fang, SY
    Sharma, RV
    Bhalla, RC
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (01) : 147 - 152