REDUCTION OF UBIQUINONE IN MEMBRANE-LIPIDS BY RAT-LIVER CYTOSOL AND ITS INVOLVEMENT IN THE CELLULAR DEFENSE SYSTEM AGAINST LIPID PEROXIDATION

被引:45
作者
TAKAHASHI, T [1 ]
YAMAGUCHI, T [1 ]
SHITASHIGE, M [1 ]
OKAMOTO, T [1 ]
KISHI, T [1 ]
机构
[1] KOBE GAKUIN UNIV,FAC PHARMACEUT SCI,NISHI KU,KOBE 65121,JAPAN
关键词
D O I
10.1042/bj3090883
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
Rat liver homogenates reduced ubiquinone (UQ)-10 to ubiquinol (UQH(2))-10 in the presence of NADPH rather than NADH. This NADPH-dependent UQ reductase (NADPH-UQ reductase) activity that was not inhibited by antimycin A and rotenone, was located mainly in the cytosol fraction and its activity accounted for 68 % of that of the homogenates. Furthermore, the NADPH-UQ reductase from rat liver cytosol efficiently reduced both UQ-10 incorporated into egg yolk lecithin liposomes, and native UQ-9 residing in rat microsomes, to the respective UQH(2) form in the presence of NADPH. The gross redox ratios of UQH(2)-9/(UQ-9 + UQH(2)-9) in individual tissues of rat correlated positively with the log of their respective cytosolic NADPH-UQ reductase activities, while the redox ratios in every intracellular fraction from liver were at about the same level, irrespective of NADPH-UQ reductase activities in the respective fractions. The combined addition of rat liver cytosol and NADPH inhibited to a great extent 2,2'-azobis(2,4-dimethyl-valeronitrile)-induced lipid peroxidation of UQ-10-fortified lecithin liposomes and completely inhibited such peroxidation in the liposomes in which UQH(2)-10 replaced UQ-10. The NADPH-UQ reductase activity was clearly separated from DT-diaphorase (EC 1.6.99.2) activity by means of Cibacron Blue-immobilized Bio-Gel A-5m chromatography. In conclusion, the NADPH-UQ reductase in cytosol, which is a novel enzyme to our knowledge, was presumed to be responsible for maintaining the steady-state redox levels of intracellular UQ and thereby to act as an endogenous antioxidant in protecting intracellular membranes from lipid peroxidation that is inevitably induced in aerobic metabolism.
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页码:883 / 890
页数:8
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