Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock.
Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock.
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DOI：
10.3164/jcbn.08-210-ho
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发表时间：
2009-01
影响因子：
2.4
通讯作者：
Morita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Takahashi, Toru;Shimizu, Hiroko;Morimatsu, Hiroshi;Maeshima, Kyoichiro;Inoue, Kazuyoshi;Akagi, Reiko;Matsumi, Masaki;Katayama, Hiroshi;Morita, Kiyoshi
失血性休克会引起氧化应激，导致肺、肝、肾和肠等多个器官的组织损伤。在氧化条件下，不稳定的血红素蛋白释放的过量游离血红素可能构成主要威胁，因为它可以催化活性氧的形成。细胞通过快速诱导血红素分解中的限速酶血红素加氧酶-1 (HO-1)（一种低分子量应激蛋白）来抵消这一影响。 HO-1 酶促反应可去除血红素。因此，失血性休克诱导的内源性 HO-1 可保护组织免受氧化剂刺激的进一步退化。此外，HO-1的预先药理诱导可改善失血性休克引起的氧化组织损伤。相反，HO-1表达的缺失或对HO活性增加的化学抑制消除了HO-1诱导的有益作用，并加剧了组织损伤。因此，HO-1 是失血性休克诱导的氧化组织损伤中重要的细胞保护成分。本文回顾了 HO-1 在失血性休克诱导的氧化组织损伤实验模型中的重要作用的最新进展，重点介绍了其诱导在组织防御中的作用。
Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.