Adaptive responses and apoptosis in endothelial cells exposed to carbon monoxide
Adaptive responses and apoptosis in endothelial cells exposed to carbon monoxide
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DOI：
10.1073/pnas.97.3.1305
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发表时间：
2000-02-01
影响因子：
11.1
通讯作者：
Ischiropoulos, H
中科院分区：
文献类型：
--
作者：
Thom, SR;Fisher, D;Ischiropoulos, H
先前的研究表明，一氧化碳(CO)暴露会增加几种细胞和人体器官中一氧化氮(NO)的稳态浓度，而且CO的一些毒性作用是针对内皮细胞的。本文报道了在空气饱和缓冲液中，牛肺动脉内皮细胞暴露于10-100ppm CO以达到11-110 nM浓度的研究。暴露于11 nM CO可增加锰超氧化物歧化酶的合成，并使其对110 nM CO的致死效应具有抵抗力。当CO浓度在88 nM或更高时，暴露1小时或更长时间会导致细胞死亡，并在停止暴露18小时后变得明显。Caspase-1被CO激活，细胞死亡被caspase-1抑制剂抑制。细胞内含有泛素的包涵体表明CO改变了细胞内的蛋白降解途径。细胞的形态变化和caspase的激活表明，细胞死亡是一个凋亡过程。一氧化氮合酶抑制剂S异丙基异硫脲和过氧亚硝酸盐清除剂蛋氨酸硒可抑制一氧化氮合酶抑制物S异丙基异硫脲和过氧亚硝酸根清除剂硒蛋氨酸对细胞抗氧化酶活性和细胞凋亡的抑制作用。这些结果表明，CO的生化效应在与环境相关的浓度下发生，细胞在暴露于相对较高浓度的CO后发生凋亡，并且这些作用是由一氧化氮介导的。
Prior studies have shown that exposure to carbon monoxide (CO) will elevate the steady-state concentration of nitric oxide (NO) in several cell types and body organs and that some toxic effects of CO are directed toward endothelial cells. Studies reported in this paper were conducted with bovine pulmonary artery endothelial cells exposed to 10 to 100 ppm CO to achieve concentrations between 11 and 110 nM in air-saturated buffer. Exposure to 11 nM CO increased synthesis of manganous superoxide dismutase and conferred resistance against the lethal effects of 110 nM CO. At concentrations of 88 nM CO or more, exposures for 1 h or longer caused cell death that became apparent 18 h after the exposure ceased. Caspase-1 was activated in response to CO, and cell death was inhibited by a caspase-1 inhibitor. Alteration of proteolytic pathways by CO was indicated by the presence of ubiquitin-containing intracellular inclusion bodies. Morphological changes and caspase activation indicated that cell death was an apoptotic process. Cells exposed to 110 nM CO had higher concentrations of manganous superoxide dismutase and heme oxygenase-1 but no changes in glutathione peroxidase, glucose-6-phosphate dehydrogenase, thiols, or catalase, Elevated levels of antioxidant enzymes and apoptosis were inhibited by the nitric oxide synthase inhibitor, S-isopropylisothiourea, and the peroxynitrite scavenger, selenomethionine. These results show that biochemical effects of CO occur at environmentally relevant concentrations, that apoptotic cell death follows exposure to relatively high concentrations of CO, and that these actions of CO are mediated by nitric oxide.