Decreased glutathione peroxidase activity in mice in response to nafenopin is caused by changes in selenium metabolism.
The activity of selenium-dependent glutathione peroxidase is known to be reduced in the liver of both rats and mice after exposure to nafenopin, as well as other peroxisome proliferators. The mechanism for this down-regulation is not known, but might involve changes in incorporation of selenium into selenoproteins. In this paper we show that both incorporation of selenium into selenoproteins and the level of selenium in liver is reduced in mice treated with nafenopin. The activity of selenium dependent glutathione peroxidase (GPx), as well as incorporation of selenium into its 23 kD subunit were found to be decreased. Contrary to what might have been expected, the decreased GPx activity was detected concomitantly with a slight increase in mRNA levels after 10 days of treatment, while a small decrease in mRNA levels was detected in treated animals after 26 weeks, together with the decrease in GPx-activity. Incorporation of selenium into liver fatty acid binding protein (L-FABP) was also decreased, even though large increases in protein and mRNA levels were detected. Taken together these data suggest that the decrease in GPx-activity in response to nafenopin is due to post-transcriptional mechanisms, involving changes in selenium metabolism.
Garberg
P
P
National Institute of Occupational Health, Department of Toxicology, Solna, Sweden.
Thullberg
M
M
D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D018996:Myelin P2 Protein / Q000378:metabolism; D009255:Nafenopin / Q000494:pharmacology*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012643:Selenium / Q000378:metabolism*; D013737:Testis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D009255:Nafenopin; D005979:Glutathione Peroxidase; D012643:Selenium