Complementary regulation of heme oxygenase-1 and peroxiredoxin I gene expression by oxidative stress in the liver.
Heme oxygenase (HO)-1, the inducible isoform of the rate-limiting enzyme of heme degradation, and peroxiredoxin (Prx) I, a thioredoxin-dependent peroxidase, are multifunctional antioxidant stress proteins which are coordinately up-regulated by oxidative stress in cell cultures. HO-1 and Prx I exhibit a different hepatic cellular and subcellular localization. Here, a distinct expression pattern of the two genes was confirmed by in situ hybridization of normal rat liver. Moreover, expression of the HO-1 and Prx I genes was determined in a model of acutely damaged rat liver which was elicited by application of a single dose of carbon tetrachloride (CCl4). The mRNA levels of the HO-1 and Prx I genes were induced in whole livers of CCl4-treated rats with differential kinetics as determined by Northern blot analysis. While HO-1 mRNA was induced up to 48 hr, Prx I exhibited a maximum level of mRNA after 12 hr of treatment with CCl4. CCl4-dependent oxidative stress led to a focal increase of perivenous HO-1 positive liver cells with simultaneous loss of Prx I immunoreactivity. Taken together, the complementary hepatic gene expression pattern of HO-1 and Prx I in response to oxidative stress may suggest a functional interplay of these antioxidant genes.
Immenschuh
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Institute for Clinical Immunology und Transfusion Medicine, University of Giessen Langhansstr. 7, 35392 Giessen, Germany. Stephan.Immenschuh@immunologie.med.uni-giessen.de
Fahimi
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HD
Baumgart-Vogt
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E
D000818:Animals; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000235:genetics*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D010544:Peroxidases / Q000032:analysis / Q000235:genetics*; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D010544:Peroxidases; D054464:Peroxiredoxins; D051547:Heme Oxygenase-1