Lee E, Miki Y, Furukawa Y, Simizu H, Kariya K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Toxicology. 1991 May;67(3):237-48. doi: 10.1016/0300-483x(91)90026-w.
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.
利用原代培养的大鼠肝细胞，研究了四氯化碳或脱氧胆酸（二者均可诱导肝毒性）对谷胱甘肽（GSH）转移酶活性的影响。用四氯化碳或脱氧胆酸处理肝细胞后，GSH转移酶的活性呈浓度和孵育时间依赖性降低。另一方面，这些化合物促使GSH转移酶的活性释放到培养基中。抗肝毒性药物甘草酸可抑制四氯化碳或脱氧胆酸诱导的天冬氨酸转氨酶（AST）和GSH转移酶的释放。这些化合物无法释放GSH转移酶的所有亚基。肝毒性释放的GSH转移酶的主要亚基被鉴定为3和4。这些结果表明，肝毒性伴随着细胞内酶活性丧失后GSH转移酶同工酶（μ类）的选择性释放。
