Defense mechanism to oxidative DNA damage in glial cells
Defense mechanism to oxidative DNA damage in glial cells
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DOI：
10.1111/j.1440-1789.2003.00540.x
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发表时间：
2004-06
期刊：
影响因子：
2.3
通讯作者：
T. Iida;A. Furuta;Y. Nakabeppu;T. Iwaki
中科院分区：
文献类型：
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作者：
T. Iida;A. Furuta;Y. Nakabeppu;T. Iwaki
星形细胞增多症是星形细胞对组织损伤反应的连续形态变化，与调节抗氧化防御机制以减少氧化损伤有关。先前报道了脑肿瘤和阿尔茨海默病神经元中氧化 DNA 损伤的修复酶、氧化嘌呤核苷三磷酸酶 (hMTH1) 和线粒体型 8-氧代鸟嘌呤 DNA 糖基化酶 (hOGG1-2a)。在本研究中，研究了这些修复酶在脑血管疾病和转移性脑肿瘤等病理条件下的神经胶质表达。此外，使用氧化应激下的神经胶质瘤细胞系进行了体外实验，以验证死后材料的免疫组织化学结果。结果，反应性星形胶质细胞中的 hOGG1-2a 免疫反应性比 hMTH1 的免疫反应性更强。脑梗塞急性或亚急性阶段的少突胶质细胞对两种修复酶均具有强烈的免疫反应性。体外研究表明，hOGG1-2a 在未处理的神经胶质瘤细胞和氧化应激下的神经胶质瘤细胞中均持续表达。然而，尽管在对照细胞中未发现对 hMTH1 的免疫反应性，但氧化应激会迅速诱导 hMTH1 的积累。这些结果表明，两种氧化DNA损伤修复酶在神经胶质细胞中受到差异性调节，并且反应性星形胶质细胞和少突胶质细胞之间修复酶的表达存在差异。
Astrocytosis is a sequential morphological change of astrocytic reaction to tissue damage, and is associated with regulation of antioxidant defense mechanisms to reduce oxidative damage. The repair enzymes to oxidative DNA damage, oxidized purine‐nucleoside triphosphatase (hMTH1) and a mitochondrial type of 8‐oxoguanine DNA glycosylase (hOGG1–2a) in brain tumors and neurons of Alzheimer's disease, were previously reported. In the present study, glial expression of these repair enzymes under such pathological conditions as cerebrovascular diseases and metastatic brain tumors, were investigated. Furthermore, an in‐vitro experiment using a glioma cell‐line under oxidative stress was performed to verify the immunohistochemical results of post‐mortem materials. As a result, hOGG1–2a immunoreactivities in reactive astrocytes were more intense than those to hMTH1. Oligodendrocytes of acute or subacute stage of brain infarction were strongly immunoreactive to both repair enzymes. In‐vitro study revealed that, hOGG1–2a is constitutively expressed in both untreated glioma cells and the glioma cells under oxidative stress. However, although no immunoreactivity to hMTH1 was found in the control cells, accumulation of hMTH1 was rapidly induced by oxidative stress. These results indicate that the two repair enzymes to oxidative DNA damage are differentially regulated in glial cells, and that there is a difference in the expression of the repair enzymes between reactive astrocytes and oligodendrocytes.