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首页> 外文期刊>Archives of Toxicology >Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide.
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Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide.

机译:过氧亚硝酸盐和一氧化氮诱导的肺上皮细胞脂质过氧化和细胞死亡机制。

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Nitric oxide (NO) is an environmental pollutant found in smog and cigarette smoke. Recently, NO has been discovered to act as a molecular messenger, mediating various physiological functions. However, when an excess of NO is present, cytotoxic and mutagenic effects can also be induced. The reaction of NO with superoxide results in the formation of peroxynitrite (ONOO(-)), which decomposes into the hydroxyl radical and nitrogen dioxide. Both of them are potent oxidant species that may initiate and propagate lipid peroxidation. In the present study, we examined the effects of NO and ONOO(-) on the induction of lipid peroxidation and cell death mechanisms in rats and in A549 pulmonary epithelial cells. The results showed that ONOO(-) is able to induce lipid peroxidation in pulmonary epithelial cells in a dose-dependent manner. 8-Epi-prostaglandin F(2)(alpha) can serve as a good biomarker of lipid peroxidation both in vitro and in vivo. Postmitotic apoptosis was found in A549 cells exposed to NO, whereas ONOO(-) induced cell death more characteristic of necrosis than apoptosis. Apoptosis that occurred in cells may be related to the dysfunction of mitochondria, the release of cytochrome c into cytosol, and the activation of caspase-9. The relationship between caspase activation and the cleavage of other death substrates during postmitotic apoptosis in A549 cells needs further investigation.
机译:一氧化氮(NO)是烟雾和香烟烟雾中的环境污染物。近来,已发现NO充当分子信使,介导各种生理功能。然而,当存在过量的NO时,也可以诱导细胞毒性和诱变作用。 NO与超氧化物的反应导致形成过氧亚硝酸盐(ONOO(-)),其分解为羟基和二氧化氮。它们都是强氧化剂,可以引发和传播脂质过氧化。在本研究中,我们检查了NO和ONOO(-)对大鼠和A549肺上皮细胞脂质过氧化诱导和细胞死亡机制的影响。结果表明ONOO(-)能够以剂量依赖的方式诱导肺上皮细胞中的脂质过氧化。 8-Epi-前列腺素F(2)α可以作为体内和体外脂质过氧化的良好生物标志物。在暴露于NO的A549细胞中发现有丝分裂后凋亡,而ONOO(-)诱导的细胞死亡比细胞凋亡更具坏死性。细胞中发生的细胞凋亡可能与线粒体功能障碍,细胞色素c释放到细胞质中以及caspase-9的活化有关。 caspase激活与A549细胞有丝分裂后细胞凋亡期间其他死亡底物的裂解之间的关系需要进一步研究。

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