Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells.
Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells.
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铁调节肺内皮细胞中高氧依赖性人血红素加氧酶 1 基因的表达。
DOI：
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发表时间：
1999
影响因子：
6.4
通讯作者：
Gary A. Visner
中科院分区：
文献类型：
--
作者：
S. Fogg;Anupam Agarwal;Harry S. Nick;Gary A. Visner
肺的内皮对氧的毒性作用敏感，并且毒性的早期证据以蛋白质渗漏和红细胞外渗为特征。氧自由基的过度产生在高氧肺损伤的病理生理学中起关键作用。血红素加氧酶1（HO-1）是血红素代谢的限速酶，近年来研究发现其在氧化损伤中具有保护作用。我们的实验室和其他人已经确定HO-1作为高氧诱导蛋白。在这项研究中，我们的特点HO-1的表达和评估其在人肺内皮细胞的调节。高氧导致HO-1表达的相对较小的增加;然而，这种诱导被血红素增强，并且在游离铁的存在下显著增强。这可能更能反映血红素和铁产物外渗的体内情况。我们还发现HO-1的表达依赖于螯合铁。铁螯合剂去铁胺不仅抑制HO-1对高氧反应的铁依赖性增强，而且抑制高氧和基础表达。在抑制剂研究和核运行试验的基础上，我们证明了这种诱导是转录依赖性的。我们还评估了4.5 kb的人HO-1启动子区域，并证明该区域具有刺激血红素的启动子活性;然而，没有证据表明启动子对铁或高氧的活性。血红素，重金属和高氧启动子活性的多样性是人类HO-1基因所独有的。
The endothelium of the lung is sensitive to the toxic effects of oxygen, and early evidence of toxicity is characterized by protein leak and extravasation of red blood cells. The overproduction of oxygen free radicals plays a critical role in the pathophysiology of a hyperoxic lung injury. Recently, heme oxygenase 1 (HO-1), the rate-limiting enzyme in the metabolism of heme, has been found to have a protective role in oxidant injury. Our laboratory and others have identified HO-1 as a hyperoxia-inducible protein. In this study, we characterized HO-1 expression and evaluated its regulation in human pulmonary endothelial cells. Hyperoxia results in a relatively small increase in HO-1 expression; however, this induction is potentiated by heme and dramatically potentiated in the presence of free iron. This is probably more reflective of the in vivo situation in which there is extravasation of heme and iron products. We also found that HO-1 expression depended on chelatable iron. The iron chelator desferrioxamine not only inhibited the iron- dependent potentiation of HO-1 in response to hyperoxia but also inhibited both hyperoxia and basal expression. On the basis of inhibitor studies and nuclear run-on assays, we demonstrated that this induction is transcriptionally dependent. We also evaluated 4.5 kb of the human HO-1 promoter region and demonstrated that this region has promoter activity to the stimulus heme; however, there was no evidence of promoter activity to either iron or hyperoxia. This diversity of promoter activity to heme, heavy metals, and hyperoxia is unique to the human HO-1 gene.
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瞬时三价铁的细胞库，可被去铁胺螯合，与铁蛋白不同，参与氧化细胞损伤。
影响因子：
3.6
作者：
Rothman,RJ;Serroni,A;Farber,JL
通讯作者：
Farber,JL
DOI：
10.1111/j.1432-1033.1997.00725.x
发表时间：
1997-07-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
McCoubrey, WK;Huang, TJ;Maines, MD
通讯作者：
Maines, MD
DOI：
10.1073/pnas.94.20.10919
发表时间：
1997-09-30
影响因子：
11.1
作者：
Poss, KD;Tonegawa, S
通讯作者：
Tonegawa, S
影响因子：
10.4
作者：
Ryan,US
通讯作者：
Ryan,US
DOI：
10.1073/pnas.93.19.10393
发表时间：
1996-09-17
影响因子：
11.1
作者：
Lee, PJ;Alam, J;Choi, AMK
通讯作者：
Choi, AMK