본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

약학회지 = Yakhak hoeji v.51 no.5, 2007년, pp.291 - 295  

인슐린 매개성 Microsomal Epoxide Hydrolase의 발현증가에서 Akt의 역할
Role of Akt in Insulin-Mediated Increase in Expression of Microsomal Epoxide Hydrolase

김상겸   (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터UU0001302  ); 김봉희   (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터UU0001302  ); 오정민   (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터UU0001302  ); 윤강욱   (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터UU0001302  ); 김충현   (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터UU0001302  ); 강건욱   (조선대학교 약학대학UU0001180  );
  • 초록

    The present study examines the effect of dominant-negative Akt on the insulin-mediated microsomal epoxide hydrolase (mEH) induction in rat hepatocytes. We also assessed the role of insulin in the expression of soluble epoxide hydrrolase (sEH). Insulin increased mEH levels and the enzyme activities, whereas sEH protein expression was unaffected by insulin. The specific PI3K inhibitors or p70 S6 kinase inhibitor ameliorated the insulin-mediated increase in mEH protein levels. Infection with adenovirus expressing dominant-negative and kinase-dead mutant of Akt1 effectively inhibited the insulin-mediated increase in mEH expression and mEH activity. These results suggest that mEH and sEH are differentially regulated by insulin and PI3K/Akt/p70S6K are active in the insulin-mediated regulation of mEH expression.


  • 주제어

    microsomal epoxide hydrolase .   soluble epoxide hydrolase .   insulin .   cellular signaling pathway .   akt.  

  • 참고문헌 (17)

    1. McGlynn, K. A., Rosvold, E. A., Lustbader, E. D., Hu, Y., Clapper, M. L., Zhou, T., Wild, C. P., Xia, X. L., Baffoe-Bonnie, A., Ofori-Adjei, D., et al. : Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin Bl. Proc. Natl. Acad. Sci. USA 92, 2384 (1995) 
    2. To-Figueras, J., Gene, M., Gomez-Catalan, J., Pique, E., Borrego, N. and Corbella, J. : Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase Pl. Cancer. Lett. 173, 155 (2001) 
    3. Sonzogni, L., Silvestri, L., De Silvestri, A., Gritti, C., Foti, L., Zavaglia, C., Bottelli, R., Mondelli, M. U., Civardi, E. and Silini, E. M.: Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease. Hepatology 36, 195 (2002) 
    4. Kim, S. K., Woodcraft, K. J., Kim, S. G. and Novak, R. E : Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes. Drug Metab. Dispos. 31, 1260 (2003) 
    5. Kim, S. K., Abdelmegeed, M. A. and Novak, R. E : Identification of the insulin signaling cascade in the regulation of alpha-class glutathione S-transferase expression in primary cultured rat hepatocytes. J. Pharmacol. Exp. Ther. 316, 1255 (2006) 
    6. Kim, S. K., Woodcraft, K. J. and Novak, R. E : Insulin and glucagon regulation of glutathione S-transferase expression in primary cultured rat hepatocytes. J. Pharmacol. Exp. Ther. 305, 353 (2003) 
    7. Kim, S. K. and Novak, R. E : The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression. Pharmacol. Ther. 113, 88 (2007) 
    8. Kim, S. K., Woodcraft, K. J., Khodadadeh, S. S. and Novak, R. E : Insulin signaling regulates gamma-glutamylcysteine ligase catalytic subunit expression in primary cultured rat hepatocytes. J. Pharmacol. Exp. Ther. 311, 99 (2004) 
    9. West, I. C. : Radicals and oxidative stress in diabetes. Diabet. Med. 17, 171 (2000) 
    10. Sies, H. : Oxidative stress: Introductory remarks. In: H. Sies, Editor, Oxidative Stress, Academic Press, San Diego, New York, London pp. 1-8 (1985) 
    11. Thomas, H., Schladt, L., Knehr, M. and Oesch, E : Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal betaoxidation. Biochem. Pharmacol. 38, 4291 (1989) 
    12. Oh, S. J., Jo, J.-H., Park, C. S., Kim, S. K. and Kim, B.-H. : Effects of the protein kinase A inhibitor KT5720 on glucagon-mediated decrease in expression of antioxidant enzymes. Journal of Environmental Toxicology 21, 245-253 (2006)     
    13. Fretland, A. J. and Omiecinski, C. J. : Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129, 41 (2000) 
    14. Baynes, J. W. and Thorpe, S. R. : Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48, 1 (1999) 
    15. Harrison, D. J., Hubbard, A. L., MacMillan, J., Wyllie, A. H. and Smith, C. A. : Microsomal epoxide hydrolase gene polymorphism and susceptibility to colon cancer. Br. J. Cancer 79, 168 (1999) 
    16. Shou, M., Gonzalez, E J. and Gelboin, H. V. : Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2 and epoxide hydrolase. Biochemistry 35, 15807 (1996) 
    17. Kim, S. K., Woodcraft, K. J., Oh, S. J., Abdelmegeed, M. A. and Novak, R. E : Role of mechanical and redox stress in activation of mitogen-activated protein kinases in primary cultured rat hepatocytes. Biochem. Pharmacol. 70, 1785 (2005) 

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • NDSL :
  • 대한약학회 : 저널
유료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기