Aniya Y, Teruya M
Laboratory of Physiology and Pharmacology, School of Health Sciences, University of the Ryukyus, Okinawa, Japan.
J Pharmacobiodyn. 1992 Sep;15(9):473-9. doi: 10.1248/bpb1978.15.473.
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.
在体内和体外研究了谷胱甘肽耗竭剂马来酸二乙酯对大鼠肝脏谷胱甘肽S-转移酶和谷胱甘肽过氧化物酶的影响。当给大鼠腹腔注射马来酸二乙酯（600mg/kg）时，肝脏谷胱甘肽在2小时内被耗尽，并在马来酸二乙酯处理后5小时恢复到对照水平。在谷胱甘肽耗竭期间，微粒体而非胞质溶胶中的谷胱甘肽S-转移酶和过氧化物酶活性均显著增加，并且在谷胱甘肽含量恢复后只有谷胱甘肽S-转移酶活性保持在高水平。通过用马来酸二乙酯（10mM）灌注离体肝脏也观察到微粒体谷胱甘肽S-转移酶和过氧化物酶活性增加，同时谷胱甘肽耗尽。当肝脏微粒体在体外37℃与马来酸二乙酯孵育时，谷胱甘肽S-转移酶活性增加，而过氧化物酶活性未增加；二硫苏糖醇不能逆转这种增加。这些结果表明，在谷胱甘肽耗竭期间，马来酸二乙酯通过与酶直接反应激活微粒体谷胱甘肽S-转移酶，并提示微粒体酶中谷胱甘肽S-转移酶活性和谷胱甘肽过氧化物酶活性可能受到不同的调节。
