Reduced glutathione is highly expressed in white matter and neurons in the unperturbed mouse brain--implications for oxidative stress associated with neurodegeneration.
Reduced glutathione is highly expressed in white matter and neurons in the unperturbed mouse brain--implications for oxidative stress associated with neurodegeneration.
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DOI：
10.1016/j.brainres.2009.04.029
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发表时间：
2009-06-18
期刊：
影响因子：
2.9
通讯作者：
Seegal RF
中科院分区：
文献类型：
--
作者：
Miller VM;Lawrence DA;Mondal TK;Seegal RF
氧化应激与许多神经退行性疾病的发病机制有关，包括帕金森病和阿尔茨海默病。谷胱甘肽（GSH）是一种强有力的抗氧化剂，它的耗尽使细胞特别容易受到氧化应激的影响.孤立的神经元和神经胶质细胞培养研究表明，神经胶质细胞，而不是神经元具有最大的储备的GSH，这意味着神经元是最敏感的氧化应激。然而，体内病理学研究表明，GSH相关酶在神经元而不是星形胶质细胞中升高。还原型谷胱甘肽的活性迅速降解，因此难以确定谷胱甘肽在死后组织中的位置。因此，为了确定GSH是否在神经元或星形胶质细胞中更高表达，我们用含有NEM的溶液灌注小鼠脑，NEM与GSH的巯基反应，从而在用抗GS-NEM抗体免疫染色之前原位锁定活性形式。我们获得了用DAPI和针对GS-NEM、胶质细胞酸性蛋白（GFAP）的抗体染色的切片的明场和荧光数字图像，所述切片在包含海马、纹状体、额叶皮质、中脑核、小脑和网状结构神经元的区域中。GSH在所有脑区的神经元和白色物质中最丰富，仅在第三和第四脑室衬里的偶尔星形胶质细胞中最丰富。神经元和白色物质中的高水平GSH表明星形胶质细胞而不是神经元可能特别容易受到氧化应激的影响。
Oxidative stress is implicated in the pathogenesis of many neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. The depletion of glutathione (GSH) a powerful antioxidant renders cells particularly vulnerable to oxidative stress. Isolated neuronal and glial cell culture studies suggest that glia rather than neurons have greatest reserves of GSH, implying that neurons are most sensitive to oxidative stress. However, pathological in vivo studies suggest that GSH associated enzymes are elevated in neurons rather than astrocytes. The active, reduced form of GSH is rapidly degraded thus making it difficult to identify the location of GSH in post-mortem tissue. Therefore, to determine whether GSH is more highly expressed in neurons or astrocytes we perfused mouse brains with a solution containing NEM which reacts with the sulfhydryl group of GSH, thus locking the active form in situ, prior to immunostaining with an anti-GS-NEM antibody. We obtained brightfield and fluorescent digital images of sections stained with DAPI and antibodies directed against GS-NEM, glial fibrillary acidic protein (GFAP) in regions containing the hippocampus, striatum, frontal cortex, midbrain nuclei, cerebellum and reticular formation neurons. GSH was most abundant in neurons and white matter in all brain regions, and only in occasional astrocytes lining the third and fourth ventricles. High levels of GSH in neurons and white matter, suggests astrocytes rather than neurons may be particularly vulnerable to oxidative stress.
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影响因子：
4.2
作者：
Dasgupta, A;Das, S;Sarkar, PK
通讯作者：
Sarkar, PK
影响因子：
3.7
作者：
Ault, JG;Lawrence, DA
通讯作者：
Lawrence, DA
影响因子：
4.3
作者：
Harry GJ;Kraft AD
通讯作者：
Kraft AD
影响因子：
3.1
作者：
Aksenov, MY;Tucker, HM;Markesbery, WR
通讯作者：
Markesbery, WR
DOI：
10.1006/faat.1997.2325
发表时间：
1997-07-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
Burchiel, SW;Kerkvliet, NL;Ladics, GS
通讯作者：
Ladics, GS