The effect of ethanol-induced CYP2E1 on proteasome activity: the role of 4-hydroxynonenal

被引:56
作者
Bardag-Gorce, F [1 ]
Li, J [1 ]
French, BA [1 ]
French, SW [1 ]
机构
[1] Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Pathol, Torrance, CA 90509 USA
关键词
ethanol feeding; CYP2E1; induction; 4-hydroxynonenal; proteasome;
D O I
10.1016/j.yexmp.2004.10.005
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Previous studies have shown that the induction of P450 cytochrome 2E1 (CYP2E1) is associated with the loss of proteasomal activities. To correlate the loss of proteasomal activity with CYP2E1 induction, ethanol was fed intragastrically for 1, 3, 7, and 15 days. The maximum induction of CYP2E1 (3.5-fold) occurred after 15 days of ethanol feeding. However, there was no significant decrease in the 26 S chymotrypsin-like and trypsin-like activity over this period of time. When ethanol was given to rats for I month, CYP2E1 was significantly induced, and the proteasomal activity was significantly decreased. These results indicate that proteasomal activity was not directly affected by ethanol or CYP2E1 induction. Since 4-hydroxynonenal (4-HNE) concentration was significantly increased at 1 month of ethanol feeding, it was suspected that 4-HNE adduct formation with proteasome subunits could be the mechanism of proteasome inhibition. Using an antibody to 4-HNE adducted proteins in Western blot analysis of the 26 S proteasome fraction isolated from the liver of alcohol fed rats, one extra band appeared around 44 kDa. When the antibody to an ATPase Rpt4 was used to stain the stripped membrane, the same band that was detected with the 4-HNE antibody was detected with the Rpt4 antibody. An adduct of 4-HNE formed with the Rpt4 subunit of 26 S could impede the association of 19 S and 20 S and thus account for the observed decrease of proteasomal activity. (c) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:109 / 115
页数:7
相关论文
共 31 条
  • [21] Acetaldehyde-modified and 4-hydroxynonenal-modified proteins in the livers of rats with alcoholic liver disease
    Li, CJ
    Nanji, AA
    Siakotos, AN
    Lin, RC
    [J]. HEPATOLOGY, 1997, 26 (03) : 650 - 657
  • [22] Mechanism of the alcohol cyclic pattern: role of the hypothalamic-pituitary-thyroid axis
    Li, J
    Nguyen, V
    French, BA
    Parlow, AF
    Su, GL
    Fu, P
    Yuan, QX
    French, SW
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2000, 279 (01): : G118 - G125
  • [23] MODULATION OF EXPERIMENTAL ALCOHOL-INDUCED LIVER-DISEASE BY CYTOCHROME-P450 2E1 INHIBITORS
    MORIMOTO, M
    HAGBJORK, AL
    WAN, YJY
    FU, PC
    CLOT, P
    ALBANO, E
    INGELMANSUNDBERG, M
    FRENCH, SW
    [J]. HEPATOLOGY, 1995, 21 (06) : 1610 - 1617
  • [24] MORIMOTO M, 1995, J NUTR, V125, P2953
  • [25] Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease
    Mottaran, E
    Stewart, SF
    Rolla, R
    Vay, D
    Cipriani, V
    Moretti, M
    Vidali, M
    Sartori, M
    Rigamonti, C
    Day, CP
    Albano, E
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (01) : 38 - 45
  • [26] Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants:: effects of acute and chronic ethanol exposure
    Navasumrit, P
    Ward, TH
    Dodd, NJF
    O'Connor, PJ
    [J]. CARCINOGENESIS, 2000, 21 (01) : 93 - 99
  • [27] 4-hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress - Identification of proteasomes as target molecules
    Okada, K
    Wangpoengtrakul, C
    Osawa, T
    Toyokuni, S
    Tanaka, K
    Uchida, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) : 23787 - 23793
  • [28] Reactions of 4-hydroxynonenal with proteins and cellular targets
    Petersen, DR
    Doorn, JA
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (07) : 937 - 945
  • [29] Laparoscopic closure of patent canal of Nuck for female indirect inguinal hernia
    Russell, JC
    [J]. JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS, 2001, 8 (01): : 10 - 11
  • [30] MICROSOMAL LIPID-PEROXIDATION - THE ROLE OF NADPH-CYTOCHROME-P450 REDUCTASE AND CYTOCHROME-P450
    SEVANIAN, A
    NORDENBRAND, K
    KIM, E
    ERNSTER, L
    HOCHSTEIN, P
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1990, 8 (02) : 145 - 152