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Differential induction of glutathione S-transferase subunits by spironolactone in rat liver, jejunum and colon.

机译:螺内酯在大鼠肝脏,空肠和结肠中对谷胱甘肽S-转移酶亚基的诱导分化。

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摘要

The effect of spironolactone pretreatment on glutathione S-transferase activity and on the relative content of the principal subunits (Ya, Yc, Yb1, Yb2 and Yp or 1, 2, 3, 4 and 7 respectively) was studied in rat liver, jejunum and colon. Male Wistar rats were injected with spironolactone i.p. at daily doses of 50, 100 and 200 micromol/kg body wt for 3 consecutive days. Glutathione S-transferase activities were assayed using 1-chloro-2,4-dinitrobenzene as substrate. Changes in subunit composition were evaluated by Western blot analysis in rats treated with the highest dose of spironolactone. The results demonstrated a dose-dependent increase in enzyme activity in liver, while in jejunum the three tested doses exhibited the same magnitude of induction. No significant difference in glutathione S-transferase activity was observed between control and treated rats for the colon. Immunoblot analysis revealed more Ya and Yp protein in liver (140 and 118% increase respectively) and jejunum (45 and 145% increase respectively) from treated rats. While Ya and Yp relative contents were similar in jejunum, the latter subunit slightly contributed to total GST in liver, even in SL-treated animals. The inducer produced no change in subunit composition in colon. In conclusion, spironolactone was able to increase glutathione S-transferase activity mainly by induction of Ya subunit in liver and Yp subunit in jejunal mucosa, without affecting colonic enzyme.
机译:研究了螺内酯预处理对大鼠肝脏,空肠和空腹谷胱甘肽S-转移酶活性以及主要亚基(Ya,Yc,Yb1,Yb2和Yp或1、2、3、4和7的相对含量)的影响。结肠。给雄性Wistar大鼠i.p.注射螺内酯。连续3天每天以50、100和200 micromol / kg体重的剂量服用。以1-氯-2,4-二硝基苯为底物测定谷胱甘肽S-转移酶活性。通过蛋白质印迹分析在用最高剂量的螺内酯治疗的大鼠中评估亚基组成的变化。结果表明,肝脏中酶活性呈剂量依赖性增加,而在空肠中,三个测试剂量均表现出相同程度的诱导。在结肠的对照和经处理的大鼠之间未观察到谷胱甘肽S-转移酶活性的显着差异。免疫印迹分析显示,处理过的大鼠肝脏中的Ya和Yp蛋白更多(分别增加140和118%)和空肠(分别增加45和145%)。空肠中Ya和Yp的相对含量相似,但后者的亚基对肝脏总GST的贡献很小,即使在SL治疗的动物中也是如此。诱导物在结肠中的亚基组成上没有变化。总之,螺内酯能够主要通过诱导肝脏中的Ya亚基和空肠黏膜中的Yp亚基来增加谷胱甘肽S-转移酶的活性,而不影响结肠酶。

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