Hepatic Metabolism of Sulfur Amino Acids During Septic Shock

패혈성 쇼크에서 간의 유황함유 아미노산 대사

  • Kang, Keon-Wook (College of Pharmacy Chosun University) ;
  • Kim, Sang-Kyum (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
  • 강건욱 (조선대학교 약학대학) ;
  • 김상겸 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터)
  • Published : 2007.12.31

Abstract

It has been reported that sulfur-containing intermediates or products in the transsulfuration pathway including S-adenosylmethionine, 5'-methylthioadenosine, glutathione and taurine can prevent liver injury mediated by inflammation response induced by lipopolysaccharide (LPS) treatment. The present study examines the modulation of hepatic metabolism of sulfur amino acid in a model of acute sepsis induced by LPS treatment (5 mg/kg, iv). Serum TNF-alpha and hepatotoxic parameters were significantly increased in rats treated with LPS, indicating that LPS results in sepsis at the doses used in this study. LPS also induced oxidative stress determined by increases in malondialdehyde levels and decreases in total oxy-radical scavenging capacities. Hepatic methionine and glutathione concentrations were decreased, but S-adenosylho-mocysteine, cystathionine, cysteine, hypotaurine and taurine concentrations were increased. Hepatic protein expression of methionine adenosyltransferase, cystathionine beta-synthase and cysteine dioxygenase were induced, but gamma-glutamylcysteine ligase catalytic subunit levels were decreased. The results show that sepsis activates transsulfuration pathway from methionine to cysteine, suggesting an increased requirement for methionine during sepsis.

Keywords

References

  1. Wagner, J. G. and Roth, R. A. : Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol. Rev. 52, 349 (2000)
  2. Seki, S., Habu, Y, Kawamura, T., Takeda, K., Dobashi, H., Ohkawa, T. and Hiraide, H.: The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses. Immunol. Rev. 174, 35 (2000)
  3. Hewett, J. A., Jean, P. A., Kunkel, S. L. and Roth, R. A. : Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin-induced liver injury. Am. J. Physiol. 265, G1011 (1993)
  4. Garcia-Alvarez, F., Navarro-Zorraquino, M., Larrad, L., Salinas, J. C, Sousa, R., Pastor, C. and Lozano, R. : S-adenosyl-methionine immunomodulator treatment in sepsis. Int. J. Surg. Investig. 2, 9 (2000)
  5. Hevia, H., Varela-Rey, M., Corrales, F. J., Berasain, C., Martinez-Chantar, M. L., Latasa, M. U., Lu, S. C, Mato, J. M., Garcia-Trevijano, E. R. and Avila, M. A. : 5'-methylthio-adenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes. Hepatology 39, 1088 (2004) https://doi.org/10.1002/hep.20154
  6. Kim, S. K. and Kim, Y. C. : Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats. Food Chem. Toxicol. 40, 545 (2002)
  7. Stipanuk, M. H. : Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu. Rev. Nutr. 24, 539 (2004) https://doi.org/10.1146/annurev.nutr.24.012003.132418
  8. Craig, S. A.: Betaine in human nutrition. Am. J. Clin. Nutr. 80, 539 (2004) https://doi.org/10.1093/ajcn/80.3.539
  9. Malmezat, T., Breuille, D., Pouyet, C., Mirand, P. P.and Obled, C.: Metabolism of cysteine is modified during the acute phase of sepsis in rats. J. Nutr. 128, 97 (1998)
  10. Malmezat, T., Breuille, D., Pouyet, C., Buffiere, C., Denis, P., Mirand, P. P. and Obled, C. : Methionine transsulfuration is increased during sepsis in rats. Am. J. Physiol. Endocrinol. Metab. 279, E1391 (2000)
  11. Kim, S. K., Choi, K. H. and Kim, Y. C.: Effect of acute betaine administration on hepatic metabolism of S-amino acids in rats and mice. Biochem. Pharmacol. 65, 1565 (2003) https://doi.org/10.1016/S0006-2952(03)00115-1
  12. Kim, S. K. and Kim, Y. C.: Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice. J. Hepatol. 42, 907 (2005) https://doi.org/10.1016/j.jhep.2005.01.017
  13. Kim, S. K., Woodcroft, K. J., Oh, S. J., Abdelmegeed, M. A. and Novak, R. F. : 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
  14. Victor, V. M., Rocha, M., Esplugues, J. V. and De la Fuente, M.: Role of free radicals in sepsis: antioxidant therapy. Curr. Pharm. Des. 11, 3141 (2005) https://doi.org/10.2174/1381612054864894
  15. Matsuzaki, Y., Sugimoto, H., Hamana, K., Nagamine, T., Matsuzaki, S. and Mori, M. : Effects of eicosanoids on lipopolysaccharide-induced ornithine decarboxylase activity and polyamine metabolism in the mouse liver. J. Hepatol. 27, 193 (1997)
  16. Hultberg, M. and Hultberg, B. : Oxidative stress decreases extracellular homocysteine concentration in human hepatoma (HepG2) cell cultures. Chem. Biol. Interact. 65, 54 (2007)
  17. Schuller-Levis, G. B. and Park, E. : Taurine: new implications for an old amino acid. FEMS Microbiol. Lett. 226, 195 (2003) https://doi.org/10.1016/S0378-1097(03)00611-6
  18. Lu, S. C.: Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J. 13, 1169 (1999)
  19. Buetler, T. M. : Identification of glutathione S-transferase isozymes and gamma-glutamylcysteine synthetase as negative acute-phase proteins in rat liver. Hepatology 28, 1551 (1998)