Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis

被引:152
作者
Iwata-Ichikawa, E [1 ]
Kondo, Y [1 ]
Miyazaki, I [1 ]
Asanuma, M [1 ]
Ogawa, N [1 ]
机构
[1] Okayama Univ, Sch Med, Inst Mol & Cellular Med, Dept Neurosci, Okayama 7008558, Japan
关键词
oxidative stress; cultured neurons; cultured glias; conditioned medium; transcriptional regulation; glutathione;
D O I
10.1046/j.1471-4159.1999.0722334.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to g-hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of gamma-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA-response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a glia conditioned medium. Neurons maintained in glia conditioned medium up-regulated the level of TRE-binding activity, gamma-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.
引用
收藏
页码:2334 / 2344
页数:11
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