In vivo reversal of glutathione deficiency and susceptibility to in vivo dexamethasone-induced apoptosis by N-acetylcysteine and L-2-oxothiazolidine-4-carboxylic acid, but not ascorbic acid, in thymocytes from gamma-glutamyltranspeptidase-deficient knocko
In vivo reversal of glutathione deficiency and susceptibility to in vivo dexamethasone-induced apoptosis by N-acetylcysteine and L-2-oxothiazolidine-4-carboxylic acid, but not ascorbic acid, in thymocytes from gamma-glutamyltranspeptidase-deficient knocko
复制标题
γ-谷氨酰转肽酶缺陷性基因敲除的胸腺细胞中，N-乙酰半胱氨酸和 L-2-氧噻唑烷-4-羧酸（而非抗坏血酸）可体内逆转谷胱甘肽缺乏和对体内地塞米松诱导的细胞凋亡的敏感性
DOI：
10.1006/abbi.2001.2662
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发表时间：
2002
影响因子：
3.9
通讯作者：
Reed,DonaldJ
中科院分区：
文献类型：
--
作者：
Will,Yvonne;Kaetzel,RhondaS;Brown,MardaK;Fraley,TamaraS;Reed,DonaldJ
细胞凋亡过程中释放谷胱甘肽，可能在线粒体通透性转换孔的调节中发挥作用。使用γ-谷氨酰转肽酶缺陷型基因敲除小鼠研究了是否只有胞质谷胱甘肽在细胞凋亡中重要，或者线粒体谷胱甘肽是否也发挥作用的问题。研究发现，这些小鼠的胸腺细胞的谷胱甘肽库均减少，并且更容易受到地塞米松 (DEX) 诱导的细胞凋亡的影响。补充 N-乙酰半胱氨酸 (NAC) 和 l -2-氧代噻唑烷-4-羧酸可补充谷胱甘肽库并提供细胞凋亡保护。补充抗坏血酸有利于线粒体谷胱甘肽库，但不能阻止细胞凋亡。补充 NAC 会导致活性氧形成和心磷脂氧化增加，但对凋亡细胞的数量没有不利影响。我们的结果表明，谷胱甘肽状态是细胞凋亡的重要因素，间接证据表明，谷胱甘肽的胞质库可能在 DEX 诱导的细胞凋亡中很重要，线粒体事件是次要的，并且可能反映执行阶段。
Cellular glutathione is released during apoptosis and may play a role in the regulation of the mitochondrial permeability transition pore. The question of whether only cytosolic glutathione is important in apoptosis, or whether mitochondrial glutathione also plays a role, was investigated using γ-glutamyltranspeptidase-deficient knockout mice. Thymocytes from these mice were found to have both glutathione pools diminished and they were more susceptible to dexamethasone (DEX)-induced apoptosis. Supplementation with N-acetylcysteine (NAC) and l -2-oxothiazolidine-4-carboxylic acid replenished both glutathione pools and provided protection from apoptosis. Ascorbate supplementation was beneficial to the mitochondrial glutathione pool, but apoptosis was not prevented. NAC supplementation caused an increase in reactive oxygen species formation and cardiolipin oxidation, but had no adverse affect on the amount of apoptotic cells. Our results suggest that the glutathione status is an important factor in apoptosis and indirect evidence indicates that the cytosolic pool of glutathione may be important in DEX-induced apoptosis, with mitochondrial events being secondary, and may reflect the execution phase.