YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Role of Akt in Insulin-Mediated Increase in Expression of Microsomal Epoxide Hydrolase

인슐린 매개성 Microsomal Epoxide Hydrolase의 발현증가에서 Akt의 역할

  • Kim, Sang-Kyum (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Bong-Hee (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Oh, Jung-Min (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Yun, Kang-Uk (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Chung-Hyeon (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kang, Keon-Wook (College of Pharmacy Chosun University)
  • 김상겸 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 김봉희 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 오정민 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 윤강욱 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 김충현 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 강건욱 (조선대학교 약학대학)
  • Published : 2007.10.31
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Abstract

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.

Keywords

References

  1. 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)
  2. West, I. C. : Radicals and oxidative stress in diabetes. Diabet. Med. 17, 171 (2000)
  3. Sies, H. : Oxidative stress: Introductory remarks. In: H. Sies, Editor, Oxidative Stress, Academic Press, San Diego, New York, London pp. 1-8 (1985)
  4. 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) https://doi.org/10.1016/j.pharmthera.2006.07.004
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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)
  10. 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)
  11. 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) https://doi.org/10.1124/dmd.31.10.1260
  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. 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) https://doi.org/10.1016/j.bcp.2005.07.019
  15. 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) https://doi.org/10.1124/jpet.105.096065
  16. 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) https://doi.org/10.1124/jpet.102.045153
  17. 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) https://doi.org/10.1124/jpet.104.070375