Correlation between Protein Methylation and Hepatotoxicity

단백질메칠화 반응과 간독성간의 상관관계

  • 김재현 (국립보건안전연구원 독성부) ;
  • 박창원 (국립보건안전연구원 독성부) ;
  • 이주한 (국립보건안전연구원 독성부) ;
  • 백윤기 (국립보건안전연구원 독성부) ;
  • 문화회 (국립보건안전연구원 독성부) ;
  • 홍성렬 (성균관대학교 유전공학과) ;
  • 이향우 (성균관대학교 약학과)
  • Published : 1994.04.01

Abstract

The methylation response as well as the level of methyl donor substance, 5-adenosyl-L-methionine (SAM) has been suggested to be related to hepatotoxicity including hepatocarcinogenesis. But direct correlation between protein methylation and hepatotoxicity has not been established to the present. To observe relationship between protein methylation and short-term hepatotoxicity induced by chemical substances, the activities of protein methylase I and II (PM I, PM II) were examined in cytosolic fraction of SD rat treated orally with acetaminophen(AA), $\alpha$-naphtyl-isothiocyanate (ANIT) and tetracycline (TC) that was known to produce necrosis, cholestasis and steatosis respectively. To evaluate the degree of hepatotoxicity induced by each chemicals, we observed the serum levels of indicative parameters and histopathological alteration. In AA treated group, the activities of PM I were increased at 6, 12 hours after administration, prior to the appearance of the hepatotoxicity by clinical parameters. It was suggested that the levels of PM I were related with the initial stage of hepatotoxic mechanism induced by AA. In ANIT treated group, though most of clinical parameters were significantly increased at 24, 48 hours after administration, the activity of PM I was not changed, indicating that ANIT induced hepatotoxicity was not coupled to protein methylation.

Keywords