Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis:: studies in vivo and in vitro
Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis:: studies in vivo and in vitro
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DOI：
10.1096/fasebj.13.9.1055
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发表时间：
1999-06-01
期刊：
影响因子：
4.8
通讯作者：
Pallardó, FV
中科院分区：
文献类型：
--
作者：
Esteve, JM;Mompo, J;Pallardó, FV
自由基可能参与细胞凋亡，尽管这是一些争议的主题。此外，凋亡细胞中自由基的来源尚不确定。本研究的目的是阐明氧化应激在分别作为体外和体内实验模型的去血清成纤维细胞培养物和断奶哺乳期乳腺细胞凋亡诱导中的作用。凋亡细胞中 mtDNA 的氧化损伤高于对照组。在细胞凋亡中，哺乳期乳腺线粒体中氧化型谷胱甘肽（GSSG）水平也较高，线粒体DNA损伤与GSSG/还原型谷胱甘肽（GSH）比率有直接关系，此外，在两种细胞凋亡模型中，全细胞GSH减少，GSSG增加，谷胱甘肽氧化先于核DNA断裂。这些氧化应激的迹象至少部分是由凋亡细胞线粒体产生的过氧化物增加引起的。我们报告了细胞凋亡中谷胱甘肽氧化和线粒体DNA损伤之间的直接关系，我们的结果支持线粒体氧化应激在诱导细胞凋亡中的作用。
Free radicals may be involved in apoptosis although this is the subject of some controversy. Furthermore, the source of free radicals in apoptotic cells is not certain. The aim of this study was to elucidate the role of oxidative stress in the induction of apoptosis in serum-deprived fibroblast cultures and in weaned lactating mammary glands as in vitro and in vivo experimental models, respectively. Oxidative damage to mtDNA is higher in apoptotic cells than in controls. Oxidized glutathione (GSSG) levels in mitochondria from lactating mammary gland are also higher in apoptosis, There is a direct relationship between mtDNA damage and the GSSG/reduced glutathione (GSH) ratio, Furthermore, whole cell GSH is decreased and GSSG is increased in both models of apoptosis, Glutathione oxidation precedes nuclear DNA fragmentation. These signs of oxidative stress are caused, at least in part, by an increase in peroxide production by mitochondria from apoptotic cells. We report a direct relationship between glutathione oxidation and mtDNA damage in apoptosis, Our results support the role of mitochondrial oxidative stress in the induction of apoptosis.