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首页> 外文期刊>American Journal of Physiology >Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione.
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Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione.

机译：一氧化氮介导的内皮细胞免受过氧化氢的保护是由细胞内锌和谷胱甘肽介导的。

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摘要

Oxidative stress may cause endothelial dysfunction and vascular disease. It has been shown that NO protects endothelial cells (EC) against H(2)O(2)-induced toxicity. In addition, it is known that NO within cells induces a zinc release from proteins containing zinc-sulfur complexes. The aim of this study was to investigate whether zinc released intracellularly by NO plays a signaling role in the NO-mediated protection against H(2)O(2) in rat aortic EC. Our results show that the NO-mediated protection toward H(2)O(2) depends on the activities of glutathione peroxidase and glutamate cysteine ligase (GCL), the rate-limiting enzyme of glutathione (GSH) de novo biosynthesis. Moreover, NO increases the synthesis of the antioxidant GSH by inducing the expression of the catalytic subunit of GCL (GCLC). Chelating intracellular "free" zinc abrogates the NO-mediated increase of GCLC and of cellular GSH levels. As a consequence, the NO-mediated protection against H(2)O(2)-induced toxicity is impaired. We also show that under proinflammatory conditions, both cellular NO synthesis and intracellular "free" zinc are required to maintain the cellular GSH levels. Using RNA interference and laser scanning microscopy, we found that the NO-induced expression of GCLC depends on the activation of the transcription factor Nrf2 but not on the activity of the "zinc-sensing" transcription factor MTF-1. These findings show that intracellular "free" zinc plays a signaling role in the protective activity of NO and could explain why maintenance of an adequate zinc status in the endothelium is important to protect from oxidative stress and the development of vascular disease.
机译：氧化应激可能导致内皮功能障碍和血管疾病。已经显示，NO保护内皮细胞（EC）免受H（2）O（2）诱导的毒性。另外，已知细胞内的NO诱导从含有锌-硫配合物的蛋白质释放锌。这项研究的目的是调查是否锌在细胞内释放的NO是否在大鼠主动脉EC的NO介导的针对H（2）O（2）的保护中起信号作用。我们的结果表明，对H（2）O（2）的NO介导保护取决于谷胱甘肽过氧化物酶和谷氨酸半胱氨酸连接酶（GCL）的活性，谷胱甘肽（GSH）从头进行生物合成的限速酶。而且，NO通过诱导GCL的催化亚基（GCLC）的表达来增加抗氧化剂GSH的合成。螯合细胞内“游离”锌消除了NO介导的GCLC和细胞GSH水平的增加。结果，对H（2）O（2）诱导的毒性NO介导的保护被削弱。我们还显示，在促炎条件下，细胞NO合成和细胞内“游离”锌都需要维持细胞GSH水平。使用RNA干扰和激光扫描显微镜，我们发现NO诱导的GCLC表达取决于转录因子Nrf2的激活，而不取决于“锌敏感”转录因子MTF-1的活性。这些发现表明，细胞内“游离”锌在NO的保护活性中起信号作用，并且可以解释为什么维持内皮中足够的锌状态对于防止氧化应激和血管疾病的发展很重要。

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