2,4-Dinitrophenol and carbonylcyanide p-trifluoromethoxyphenylhydrazone activate the glutathione S-conjugate transport ATPase of human erythrocyte membranes.
2,4-Dinitrophenol and carbonylcyanide p-trifluoromethoxyphenylhydrazone activate the glutathione S-conjugate transport ATPase of human erythrocyte membranes.
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2,4-二硝基苯酚和羰基氰化物对三氟甲氧基苯腙可激活人红细胞膜的谷胱甘肽 S-缀合物转运 ATP 酶。
DOI：
10.1006/abbi.1994.1406
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发表时间：
1994
影响因子：
3.9
通讯作者：
Szumilo,H
中科院分区：
文献类型：
--
作者：
Winter,CG;DeLuca,DC;Szumilo,H
2，4-二硝基苯酚（DNPOH）和羰基氰对三氟甲氧基苯腙（FCCP）是线粒体氧化磷酸化的两种经典解偶联剂。这两种化合物与S-（2，4-二硝基苯基）谷胱甘肽（DNPSG）竞争激活谷胱甘肽S-共轭转运ATP酶。DNPOH或FCCP对ATP酶的刺激作用最大值比DNPSG大4-6倍。DNPOH（195 μM）的K_（0.5）与DNPSG（196 μM）相似，而FCCP（4.3 μM）的K_（0.5）低40倍。钒酸盐抑制DNPOH和FCCP刺激的ATP酶活性，如先前报道的谷胱甘肽S-缀合物ATP酶。这些经典解偶联剂对红细胞囊泡ATP酶活性的刺激不是由于增加了穿过囊泡膜的质子电导引起的：莫能菌素、短杆菌肽和制霉菌素，所有这些都增加了质子电导，但通过不同的机制，不刺激红细胞囊泡ATP酶活性。维拉帕米是一种已知的P-糖蛋白ATP酶激活剂，也不刺激人红细胞膜ATP酶活性。这些结果表明，相对较小的单阴离子亲脂性化合物如DNPOH和FCCP可激活谷胱甘肽S-缀合物转运ATP酶。这些试剂激活的Vmax值高于DNPSG，这使得对这种转运ATP酶活性的更灵敏的测定成为可能。结果提出了一个问题：这些物质和其他小的阴离子亲脂性化合物是否也可以通过该系统运输。
2,4-Dinitrophenol (DNPOH) and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), two classical uncouplers of mitochondrial oxidative phosphorylation, were found to stimulate human erythrocyte membrane vesicle ATPase activity. Both compounds competed withS-(2,4-dinitrophenyl) glutathione (DNPSG) for activation of the glutathione S-conjugate transport ATPase. Stimulation of the ATPase by DNPOH or FCCP occurred withVmaxvalues 4-6 times greater than that with DNPSG. TheK0.5for DNPOH (195 μM) was similar to that of DNPSG (196 μM), while that for FCCP (4.3 μM) was 40 times lower. Vanadate inhibits both the DNPOH- and FCCP-stimulated ATPase activities, as previously reported for the glutathione S-conjugate ATPase. The stimulation of erythrocyte vesicle ATPase activities by these classical uncoupling agents does not result from increased proton conductance across the vesicle membrane: monensin, gramicidin and nystatin, all of which increase proton conductance, but by different mechanisms, do not stimulate erythrocyte vesicle ATPase activity. Verapamil, a known P-glycoprotein ATPase activator also does not stimulate human erythrocyte membrane ATPase activity. These results show that relatively small, monoanionic lipophilic compounds such as DNPOH and FCCP can activate the glutathione S-conjugate transport ATPase. The higherVmaxvalues for activation by these agents than by DNPSG make possible a more sensitive assay of this transport ATPase activity. The results raise the question of whether these substances and other small anionic, lipophilic compounds are also transported by this system.