Induction and peroxisomal appearance of gulonolactone oxidase upon clofibrate treatment in mouse liver

FEBS Letters

Mile, Valéria¹  Schaff, Zsuzsa²  Braun, László¹  Kardon, Tamás¹  Csala, Miklós¹  Bánhegyi, Gábor¹  Mandl, József¹ 

[1] Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary;First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary

关键词: Clofibrate;    Peroxisome;    Gulonolactone oxidase;    H2O2;    Ascorbate;   

DOI  :  10.1016/S0014-5793(99)01184-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Various antihyperlipemic peroxisome proliferators are known to be carcinogenic in rodents but not in human, other primates and guinea pig, which species lost their ability to synthesize ascorbate due to mutations in the gulonolactone oxidase gene. Ascorbate synthesis is accompanied by H₂O₂ production, consequently its induction can be potentially harmful; therefore, the in vivo effect of the peroxisome proliferator clofibrate was investigated on gulonolactone oxidase expression in mouse liver. Liver weights and peroxisomal protein contents were increased upon clofibrate treatment. Elevated plasma ascorbate concentrations were found in clofibrate-treated mice due to the higher microsomal gulonolactone oxidase activities. Remarkable gulonolactone oxidase activity appeared in the peroxisomal fraction upon the treatment. Increased activity of the enzyme was associated with an elevation of its mRNA level. According to the present results the evolutionary loss of gulonolactone oxidase may contribute to the explanation of the missing carcinogenic effect of peroxisome proliferators in humans.

【 授权许可】

Unknown