Activation of hepatic microsomal glutathione S-transferase of rats by a glutathione depletor, diethylmaleate.
The effect of glutathione depletor diethylmaleate on rat hepatic glutathione S-transferase and glutathione peroxidase was studied in vivo and in vitro. When diethylmaleate (600 mg/kg) was given i.p. to rats, liver glutathione was depleted within 2 h and recovered to the control level 5 h after diethylmaleate treatment. Both glutathione S-transferase and peroxidase activities in microsomes, not in cytosol, were markedly increased during glutathione depletion and only glutathione S-transferase activity remained at high levels after recovery of the glutathione content. The increase in microsomal glutathione S-transferase and peroxidase activities with concomitant exhaustion of glutathione was also observed by perfusion of the isolated liver with diethylmaleate (10 mM). When liver microsomes were incubated with diethylmaleate in vitro at 37 degrees C, glutathione S-transferase, but not peroxidase, activity was increased; the increase was not reversed by dithiothreitol. These results indicate that diethylmaleate activates microsomal glutathione S-transferase by direct reaction to the enzyme during glutathione depletion and suggest that glutathione S-transferase activity and glutathione peroxidase activity in the microsomal enzyme may be differently regulated.
Aniya
Y
Y
Laboratory of Physiology and Pharmacology, School of Health Sciences, University of the Ryukyus, Okinawa, Japan.
Teruya
M
M
D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000172:deficiency*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014357:Trypsin / Q000494:pharmacology
D008298:Maleates; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D014357:Trypsin; C014476:diethyl maleate; D005978:Glutathione; D004229:Dithiothreitol