The activation of microsomal glutathione
S-transferase in oxidative stress was investigated by perfusing isolated rat liver with 1 mM
tert-butyl hydroperoxide (
t-BuOOH). When the isolated liver was perfused with
t-BuOOH for 7 min and 10 min, microsomal, but not cytosolic, glutathione
S-transferase activity was increased 1.3-fold and 1.7-fold, respectively, with a concomitant decrease in glutathione content. A dimer protein of microsomal glutathione
S-transferase was also detected in the
t-BuOOH-perfused liver. The increased microsomal glutathione
S-transferase activity after perfusion with
t-BuOOH was reversed by dithiothreitol, and the dimer protein of the transferase was also abolished. When the rats were pretreated with the antioxidant α-tocopherol or the iron chelator deferoxamine, the increases in microsomal glutathione
S-transferase activity and lipid peroxidation caused by
t-BuOOH perfusion of the isolated liver was prevented. Furthermore, the activation of microsomal GSH
S-transferase by
t-BuOOH in vitro was also inhibited by incubation of microsomes with α-tocopherol or deferoxamine. Thus it was confirmed that liver microsomal glutathione
S-transferase is activated in the oxidative stress caused by
t-BuOOH via thiol oxidation of the enzyme.
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