Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease.
Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease.
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DOI：
10.1016/j.freeradbiomed.2009.04.007
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发表时间：
2009-07-01
影响因子：
7.4
通讯作者：
Ryter, Stefan W.
中科院分区：
文献类型：
--
作者：
Morse, Danielle;Lin, Ling;Choi, Augustine M. K.;Ryter, Stefan W.
增加细胞死亡的程序（即，凋亡，自噬）或非程序性机制（即，坏死）发生在组织损伤期间，并且可能导致几种肺或血管疾病状态的病因。低分子量应激蛋白血红素加氧酶-1（HO-1）通过抑制细胞凋亡、炎症和细胞增殖，在各种肺和血管损伤模型中赋予细胞保护作用，以对抗细胞死亡。HO-1作为血红素降解途径中的限速步骤和维持铁稳态的重要代谢功能。HO-1的转录诱导响应于多种形式的化学和物理细胞应激而发生。HO-1的细胞保护功能可能归因于血红素周转，以及其酶促反应产物的有益特性：胆绿素-IX α、铁和一氧化碳（CO）。最近的研究表明，HO-1或CO抑制体外应激诱导的外源性和内源性凋亡途径。HO-1/CO的细胞保护作用涉及多种信号分子，包括自噬蛋白、p38丝裂原活化蛋白激酶、信号转导和转录激活蛋白、核因子-κB、磷酸肌醇-3-激酶/Akt等。HO-1表达增强或HO终产物的药理学应用在组织损伤的临床前模型中提供保护，包括实验性和移植相关的缺血/再灌注损伤，有希望的潜在未来治疗应用。
Increases in cell death by programmed (ie., apoptosis, autophagy) or non-programmed mechanisms (ie., necrosis) occur during tissue injury, and may contribute to the etiology of several pulmonary or vascular disease states. The low molecular weight stress protein heme oxygenase-1 (HO-1) confers cytoprotection against cell death in various models of lung and vascular injury by inhibiting apoptosis, inflammation, and cell proliferation. HO-1 serves a vital metabolic function as the rate-limiting step in the heme degradation pathway and in the maintenance of iron homeostasis. The transcriptional induction of HO-1 occurs in response to multiple forms of chemical and physical cellular stress. The cytoprotective functions of HO-1 may be attributed to heme turnover, as well as to beneficial properties of its enzymatic reaction products: biliverdin-IXα, iron, and carbon monoxide (CO). Recent studies have demonstrated that HO-1 or CO inhibits stress-induced extrinsic and intrinsic apoptotic pathways in vitro. A variety of signaling molecules have been implicated in the cytoprotection conferred by HO-1/CO, including autophagic proteins, p38 mitogen activated protein kinase, signal transducer and activator of transcription proteins, nuclear factor-κB, phosphatydylinositol-3-kinase/Akt, and others. Enhanced HO-1 expression or the pharmacological application of HO end-products affords protection in preclinical models of tissue injury, including experimental and transplant-associated ischemia/reperfusion injury, promising potential future therapeutic applications.
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影响因子：
7.4
作者：
Choi, BM;Pae, HO;Chung, HT
通讯作者：
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作者：
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DOI：
10.1073/pnas.172398899
发表时间：
2002-09-03
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DOI：
10.1165/rcmb.2006-0340tr
发表时间：
2007-02-01
影响因子：
6.4
作者：
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通讯作者：
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DOI：
10.1152/ajprenal.00215.2004
发表时间：
2005-04-01
影响因子：
4.2
作者：
Adin, CA;Croker, BP;Agarwal, A
通讯作者：
Agarwal, A