Ethanol and arachidonic acid increase α2(I) collagen expression in rat hepatic stellate cells overexpressing cytochrome P450 2E1 -: Role of H2O2 and cyclooxygenase-2

被引:101
作者
Nieto, N
Greenwel, P
Friedman, SL
Zhang, F
Dannenberg, AJ
Cederbaum, AI
机构
[1] Mt Sinai Sch Med, Dept Biochem & Mol Biol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Med & Liver Dis, New York, NY 10029 USA
[3] Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY 10021 USA
[4] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA
[5] Strang Canc Prevent Ctr, New York, NY 10021 USA
关键词
D O I
10.1074/jbc.M001422200
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
The ability of ethanol and arachidonic acid (AA), as inducers of oxidative stress and key factors in alcoholic liver disease, to up-regulate alpha 2 collagen type I (COL1A2) gene expression was studied in a hepatic stellate cell line overexpressing the ethanol-inducible cytochrome P450 2E1 (CYP2E1) (E5 cells). A time- and dose-dependent induction in COL1A2 mRNA by ethanol or AA was observed that was prevented by diallylsulfide, a CYP2E1 inhibitor, Nuclear run-on experiments showed transcriptional activation of the COL1A2 gene by ethanol and Ak Catalase abrogated the increase in COL1A2 mRNA suggesting an H2O2-dependent mechanism. Cyclooxygenase-2 (COX-2) levels and production of prostaglandin E-2 upon addition of AA were elevated in the E5 cells. Incubation with NS-398, a COX-2 inhibitor, blocked the effect of AA, but not of ethanol, on COL1A2 expression suggesting that CYP2E1 activates COX-2 expression, and the oxidation of AA by COX-2 is responsible for the increase in COL1A2. Activity of a reporter construct driven by -378 base pairs of the proximal promoter region of the COL1A2 gene increased in E5 but not control cells and was further increased by ethanol or AA. These experiments link CYP2E1-dependent oxidative stress to induction of COX-2 and the actions of ethanol and AA on activation of collagen gene expression in hepatic stellate cells.
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页码:20136 / 20145
页数:10
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共 62 条
  • [1] Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2
    Adderley, SR
    Fitzgerald, DJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (08) : 5038 - 5046
  • [2] Albano E, 1996, HEPATOLOGY, V23, P155, DOI 10.1053/jhep.1996.v23.pm0008550035
  • [3] Albano Emanuele, 1999, Frontiers in Bioscience, V4, pd533, DOI 10.2741/Albano
  • [4] BEDOSSA P, 1994, HEPATOLOGY, V19, P1262, DOI 10.1016/0270-9139(94)90876-1
  • [5] BOAST S, 1990, J BIOL CHEM, V265, P13351
  • [6] Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats
    Boigk, G
    Stroedter, L
    Herbst, H
    Waldschmidt, J
    Riecken, EO
    Schuppan, D
    [J]. HEPATOLOGY, 1997, 26 (03) : 643 - 649
  • [7] INHIBITION OF CYTOCHROME-P-450 2E1 BY DIALLYL SULFIDE AND ITS METABOLITES
    BRADY, JF
    ISHIZAKI, H
    FUKUTO, JM
    LIN, MC
    FADEL, A
    GAPAC, JM
    YANG, CS
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 1991, 4 (06) : 642 - 647
  • [8] BRENNER DA, 1987, J BIOL CHEM, V262, P17690
  • [9] CARTER WO, 1994, J LEUKOCYTE BIOL, V55, P253
  • [10] Casini A, 1997, HEPATOLOGY, V25, P361