Selective release of glutathione transferase subunits from primary cultured rat hepatocytes by carbon tetrachloride and deoxycholic acid.
The change in the activity of glutathione (GSH) transferases by carbon tetrachloride or deoxycholic acid, which induced hepatotoxicity, was studied using primary cultured rat hepatocytes. The activity of GSH transferases in the hepatocytes was decreased after the treatment with carbon tetrachloride or deoxycholic acid in their concentration- and incubation time-dependent manners. On the other hand, these compounds elicited the release of the activity of GSH transferases into the medium. Glycyrrhizin, an antihepatotoxic agent, inhibited the release of both aspartate transaminase (AST) and GSH transferases induced by carbon tetrachloride or deoxycholic acid. All subunits comprised of GSH transferases could not be released by these compounds. The main subunits of GSH transferases released by hepatotoxicity were identified as 3 and 4. These results indicate that hepatotoxicity is accompanied by the selective release of GSH transferase isozymes (class mu) following the loss of the enzymes activity in the cells.
Lee
E
E
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Miki
Y
Y
Furukawa
Y
Y
Simizu
H
H
Kariya
K
K
D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D003840:Deoxycholic Acid / Q000633:toxicity*; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D013379:Substrate Specificity
D003470:Culture Media; D007527:Isoenzymes; D003840:Deoxycholic Acid; D019695:Glycyrrhizic Acid; D002251:Carbon Tetrachloride; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D006034:Glycyrrhetinic Acid