Oxidative stress-induced activation of microsomal glutathione S-transferase in isolated rat liver

Biochem Pharmacol. 1993 Jan 7;45(1):37-42. doi: 10.1016/0006-2952(93)90374-6.


The activation of microsomal glutathione (GSH) S-transferase in isolated rat liver by oxidative stress was investigated using both ischemia/reperfusion and perfusion with hydrogen peroxide. When the isolated liver was reperfused for 30 min and 60 min after 90 min ischemia, microsomal GSH S-transferase activity, but not cytosolic transferase activity, was increased 1.2-fold and 1.3-fold, respectively. In addition, microsomal GSH peroxidase activity was also significantly increased after 60 min reperfusion following ischemia. The increase in microsomal GSH S-transferase activity by ischemia/reperfusion was reversed by dithiothreitol. When N-ethylmaleimide, which activates microsomal GSH S-transferase by covalent binding to the cysteine residue of the enzyme, was incubated with microsomes, transferase activity was increased to 526% in control microsomes and to 399% in liver that underwent ischemia/reperfusion liver. These data indicate that microsomal GSH S-transferase is activated by ischemia/reperfusion of the liver by means of disulfide bond formation. When rats were pretreated with a catalase inhibitor 3-amino-1,2,4-triazole for 6 weeks, microsomal GSH S-transferase activity was increased 1.4-fold by ischemia/reperfusion, corresponding to a 1.8-fold increase as compared to the non-perfused liver of untreated rats. Perfusion of the isolated liver with hydrogen peroxide (1 mM, 15 min) also caused a significant increase in microsomal GSH S-transferase activity with a concomitant decrease in GSH content, confirming that liver microsomal GSH S-transferase in rats was activated in vivo by oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dithiothreitol / pharmacology
  • Enzyme Activation / drug effects
  • Ethylmaleimide / pharmacology
  • Free Radicals
  • Glutathione Transferase / metabolism*
  • Hydrogen Peroxide / pharmacology
  • Ischemia / metabolism
  • Liver / blood supply
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Oxidation-Reduction
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / metabolism


  • Free Radicals
  • Hydrogen Peroxide
  • Glutathione Transferase
  • Ethylmaleimide
  • Dithiothreitol