Effects of the peroxisome proliferator clofibric acid on superoxide dismutase expression in the human HepG2 hepatoma cell line.
We examined the effects of clofibric acid, a peroxisome proliferator, on the production of superoxide radicals, on the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and on the expression of superoxide dismutases (SODs) in the human HepG2 hepatoma cell line. To this end, HepG2 cells were treated for 1 or 5 days with 0.25, 0.50, or 0.75 mM clofibric acid. The production of superoxide radicals was only enhanced in HepG2 cells exposed for 5 days to the different clofibric acid concentrations. However, this overproduction of superoxide radicals was not accompanied by increased rates of lipid peroxidation, as the MDA and 4-HNE levels did not change significantly. Manganese (Mn) SOD activity was increased when HepG2 cells were treated for 1 day with 0.50 or 0.75 mM clofibric acid. For this duration of treatment, no change was observed in total SOD and copper/zinc (Cu/Zn) SOD activities. For a 5-day treatment, total SOD and MnSOD activities as well as the enzyme apoprotein and MnSOD mRNA levels increased whatever the clofibric acid concentration used. This transcriptional induction of the MnSOD gene was correlated with an activation of the activator protein-1 transcription factor for 1 and 5 days of treatment, but was independent of nuclear factor-kappa B and of peroxisome proliferator-activated receptor. On the other hand, the PP exerted very little effect if any on Cu,ZnSOD expression. In contrast to rodent data, PP treatment of human hepatoma cells induces MnSOD expression.
Bécuwe
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Laboratoire de Biologie Cellulaire du Developpement, Upres 2402 Proliferateurs de Peroxysomes, Universite Henri Poincare Nancy I, Faculte des Sciences, Vandoeuvre-les-Nancy, France. becuwe@scbiol.u-nancy.fr
Bianchi
A
A
Keller
J M
JM
Dauça
M
M
D001059:Apoproteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D002995:Clofibric Acid / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001059:Apoproteins; D016328:NF-kappa B; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D013481:Superoxides; D002995:Clofibric Acid; D004247:DNA; D013482:Superoxide Dismutase