Hydrogen sulfide protects neurons from oxidative stress

Hydrogen sulfide protects neurons from oxidative stress
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DOI:
10.1096/fj.04-1815fje
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发表时间:
2004-05-01
期刊:
影响因子:
4.8
通讯作者:
Kimura, H
Kimura, H
中科院分区:
生物学2区
文献类型:
--
作者:
Kimura, Y;Kimura, H

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硫化氢是一种众所周知的有毒气体,在大脑中发现浓度相对较高。虽然硫化氢的神经调节作用已被证明,但对其其他生物学功能知之甚少。在这里,我们证明了在一个由谷氨酸引起的氧化应激模型中,硫化氢保护原代培养的神经元免于死亡,这个过程被称为氧化谷氨酸毒性-或催产素。我们发现,硫化氢通过增强γ-谷氨酰半胱氨酸合成酶的活性和上调半胱氨酸的运输,增加了谷胱甘肽水平,而谷胱甘肽水平在细胞死亡级联过程中通常会下降。半胱氨酸是谷胱甘肽合成的限速底物。这些观察表明,硫化氢通过增加抗氧化剂谷胱甘肽的产生来保护神经元免受催产素的影响。
Hydrogen sulfide (H2S), which is a well-known toxic gas, is found in relatively high concentrations in the brain. Although a neuromodulatory role of H2S has been demonstrated, little is known of its other biological functions. Here we show that H2S protects primary cultures of neurons from death in a well-studied model of oxidative stress caused by glutamate, a process called oxidative glutamate toxicity - or oxytosis. We found that H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of gamma-glutamylcysteine synthetase and up-regulating cystine transport. Cystine ( cysteine) is the rate-limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione.