Glutathione distribution in normal and oxidatively stressed cells

Glutathione distribution in normal and oxidatively stressed cells
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DOI:
10.1016/s0014-4827(03)00012-0
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发表时间:
2003-04-15
影响因子:
3.7
通讯作者:
Lawrence, DA
Lawrence, DA
中科院分区:
医学3区
文献类型:
--
作者:
Ault, JG;Lawrence, DA

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谷胱甘肽是最丰富的低分子质量分子,提供还原等价物,保护细胞免受氧化应激。我们用免疫电镜观察正常细胞和氧化应激细胞中谷胱甘肽的分布。在这里,我们首次表明还原性谷胱甘肽在整个细胞中分布相对均匀,除了粗内质网的管腔外,在那里几乎没有检测到。氧化暴露,无论是0.1毫米二胺或乙辛酸,最终导致细胞谷胱甘肽耗竭。然而,尽管在几秒钟内进入细胞,但这两种氧化剂都需要数小时才能显著影响人群中大多数细胞中的谷胱甘肽水平。有趣的是,同质细胞系群体中的细胞以不同的速率丢失谷胱甘肽。与氧化应激相关的结构变化,如空泡化和膜起泡的增加,与谷胱甘肽耗竭有关。暴露在氧化剂下的正常细胞的谷胱甘肽水平高于同一人群中表现出压力的细胞。细胞谷胱甘肽的最后储备是在线粒体内发现的。(C) 2003 Elsevier Science(美国)版权所有。
Glutathione is the most abundant of the low-molecular-mass molecules that provide reducing equivalents that protect cells from oxidative stress. We used immunoelectron microscopy to investigate glutathione distribution in normal and oxidatively stressed cells. Here, for the first time, we show that reduced glutathione is distributed relatively evenly throughout the cell, with the exception of the lumen of the rough endoplasmic reticulum, where little is detected. Oxidant exposure, either to 0.1 mM diamide or ethycrinic acid, eventually caused cellular glutathione depletion. However, despite entering a cell within seconds, both oxidants required hours to dramatically affect glutathione levels in the majority of cells in a population. Interestingly, cells within a homogeneous cell line population lost glutathione at different rates. Structural changes associated with oxidative stress, such as increased vacuolization and membrane blebbing, were correlated with glutathione depletion. Oxidant-exposed cells that appeared normal had higher glutathione levels than those within the same population that appeared stressed. The last reserves of cellular glutathione were found within mitochondria. (C) 2003 Elsevier Science (USA). All rights reserved.