Olson C E, Soll A H, Kaplowitz N
J Biol Chem. 1985 Jul 5;260(13):8020-5.
Thiol-oxidizing agents were found to stimulate [14C] aminopyrine accumulation, a reliable index of acid secretory function of isolated canine parietal cells. Glutathione is the predominant intracellular free thiol; thus, its oxidation status largely determines the thiol-disulfide status of the cell by thiol-disulfide interchange reactions. Three agents which alter glutathione oxidation status by different mechanisms were applied to parietal cells in vitro to investigate whether enhanced formation of GSSG alters acid secretory function. The agents studied were diamide (which nonenzymatically oxidizes GSH to GSSG), tert-butyl hydroperoxide (an organic peroxide specifically reduced by glutathione peroxidase, thereby generating GSSG for GSH), and 1,3-bis(2-chloroethyl)-1-nitrosourea (an inhibitor of NADPH:GSSG reductase, which presumably allows the accumulation of GSSG). Each of these agents stimulated aminopyrine accumulation in a dose-dependent fashion. Simple depletion of GSH by diethyl maleate or 2-cyclohexene-1-one did not stimulate aminopyrine accumulation. Likewise, enhanced aminopyrine accumulation occurred at diamide concentrations which did not cause significant depletion of total cellular glutathione. The thiol-reducing agent, dithiothreitol, prevented enhanced aminopyrine accumulation by 1,3-bis(2-chloroethyl)-1-nitrosourea and tert-butyl hydroperoxide. These observations support the hypothesis that thiol-disulfide interchange reactions involving GSSG modulate the acid secretory function of the isolated parietal cell.
硫醇氧化剂被发现可刺激[14C]氨基比林的蓄积，这是分离的犬壁细胞酸分泌功能的可靠指标。谷胱甘肽是细胞内主要的游离硫醇；因此，其氧化状态通过硫醇-二硫键交换反应在很大程度上决定了细胞的硫醇-二硫键状态。应用三种通过不同机制改变谷胱甘肽氧化状态的试剂于体外壁细胞，以研究GSSG形成增加是否会改变酸分泌功能。所研究的试剂为二酰胺（它非酶促地将GSH氧化为GSSG）、叔丁基过氧化氢（一种被谷胱甘肽过氧化物酶特异性还原的有机过氧化物，从而为GSH生成GSSG）和1,3-双(2-氯乙基)-1-亚硝基脲（一种NADPH:GSSG还原酶抑制剂，推测可使GSSG蓄积）。这些试剂中的每一种都以剂量依赖的方式刺激氨基比林的蓄积。马来酸二乙酯或2-环己烯-1-酮简单地耗尽GSH并不会刺激氨基比林的蓄积。同样，在二酰胺浓度下氨基比林蓄积增加，而该浓度并未导致细胞总谷胱甘肽显著耗尽。硫醇还原剂二硫苏糖醇可阻止1,3-双(2-氯乙基)-1-亚硝基脲和叔丁基过氧化氢引起的氨基比林蓄积增加。这些观察结果支持这样的假说，即涉及GSSG的硫醇-二硫键交换反应调节分离的壁细胞的酸分泌功能。
