Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism
Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism
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DOI：
10.1096/fj.08-128926
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发表时间：
2009-08-01
期刊：
影响因子：
4.8
通讯作者：
Gaylor, David W.
中科院分区：
文献类型：
--
作者：
James, S. Jill;Rose, Shannon;Gaylor, David W.
尽管代谢异常与其他几种神经行为障碍的病理生理学有关，但对自闭症代谢表型的研究相对较少。已有关于自闭症儿童氧化应激血浆生物标志物的报道；然而，细胞内氧化还原状态尚未得到评估。利用来自自闭症儿童和未受影响对照组的淋巴母细胞（LCLs）来评估细胞提取物和分离的线粒体中还原型谷胱甘肽（GSH）和氧化型二硫键谷胱甘肽（GSSG）的相对浓度，以此作为细胞内氧化还原能力的衡量指标。结果表明，在自闭症LCLs中，细胞质和线粒体中的GSH/GSSG氧化还原比均降低，氧化型谷胱甘肽百分比增加。与对照细胞相比，通过巯基试剂硫柳汞暴露于氧化应激下，导致自闭症细胞中GSH/GSSG比更大幅度地降低以及自由基产生增加。急性暴露于生理水平的一氧化氮使自闭症LCLs的线粒体膜电位降低程度更大，尽管两种细胞系中的GSH/GSSG和ATP浓度都有类似降低。这些结果表明，自闭症LCLs在细胞质和线粒体中都表现出谷胱甘肽储备能力降低，这可能在促氧化条件下损害抗氧化防御和解毒能力。——詹姆斯，S.J.，罗斯，S.，梅尔尼克，S.，杰尼根，S.，布洛瑟姆，S.，帕夫利夫，O.，盖洛，D.W. 自闭症儿童来源的淋巴母细胞中细胞和线粒体谷胱甘肽氧化还原失衡。《美国实验生物学会联合会杂志》23，2374 - 2383（2009年）
Research into the metabolic phenotype of autism has been relatively unexplored despite the fact that metabolic abnormalities have been implicated in the pathophysiology of several other neurobehavioral disorders. Plasma biomarkers of oxidative stress have been reported in autistic children; however, intracellular redox status has not yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG) in cell extracts and isolated mitochondria as a measure of intracellular redox capacity. The results indicated that the GSH/GSSG redox ratio was decreased and percentage oxidized glutathione increased in both cytosol and mitochondria in the autism LCLs. Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.-James, S. J., Rose, S., Melnyk, S., Jernigan, S., Blossom, S., Pavliv, O., Gaylor, D. W. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J. 23, 2374-2383 (2009)