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首页> 外文期刊>Journal of Cellular Physiology >Hypoxia decreases constitutive nitric oxide synthase transcript and protein in cultured endothelial cells.
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Hypoxia decreases constitutive nitric oxide synthase transcript and protein in cultured endothelial cells.

机译:缺氧减少本构一氧化氮在培养合酶转录和蛋白质内皮细胞。

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摘要

Endothelial cell-generated nitric oxide (NO) accounts in large part for the labile vasodilator termed endothelium-derived relaxing factor. Two distinct types of NO synthase exist: a "constitutive' type (cNOS), found in endothelial cells, and an "inducible' enzyme. Endothelial cells sense pO2 levels in the range of 70-20 torr and respond to this hypoxia by inducing transcription of genes which encode the vasoactive proteins PDGF-B and endothelin-1. Exposure of human or bovine endothelial cells to low oxygen tensions results in a profound decrease in the transcript for cNOS and a corresponding fall in cNOS protein levels. The ability of endothelial cells exposed to hypoxia to produce NO in response to bradykinin, a stimulator of cNOS activity, was coordinately impaired. Cobalt inhibited the expression of cNOS transcripts, suggesting a mechanism comparable to that by which oxygen tension regulates expression of other vasoregulatory genes. In the presence of actinomycin-D, hypoxia had no effect on cNOS transcripts, suggesting that new gene transcription is required for cNOS suppression. The reducing agents PDTC and N-Ac did not mimic cNOS gene suppression by hypoxia, suggesting that this suppression is not related to the redox state of the intracellular environment. Thus, regulation of cNOS function in response to environmental factors can occur at the level of gene expression as well as at the level of enzyme activation.
机译:内皮cell-generated一氧化氮(NO)账户在很大程度上不稳定血管舒张称为endothelium-derived放松的因素。不同类型的不存在合酶:a“本构的类型(碳氮氧),内皮中找到细胞,和一个“诱导酶。细胞感觉警察乙水平在70 - 20托和应对缺氧诱导转录的基因编码血管活性的蛋白质PDGF-B和endothelin-1。接触人或牛内皮细胞低氧导致深刻的紧张关系减少对碳氮氧和成绩单碳氮氧蛋白质含量相应下降。内皮细胞暴露于低氧的能力生产没有缓激肽,刺激器的碳氮氧活动,协调受损。成绩单,暗示与机制氧张力调节的表达式其他vasoregulatory基因。放线菌素d,对碳氮氧缺氧没有影响成绩单,这表明新基因对碳氮氧抑制转录是必需的。减少代理PDTC N-Ac并没有模仿碳氮氧基因抑制缺氧,这表明这抑制与氧化还原细胞内环境的状态。调节碳氮氧功能响应环境因素可能发生的基因表达以及酶的水平激活。

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