The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury.
The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury.
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DOI：
10.1152/ajprenal.00297.2003
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发表时间：
2004-03
期刊：
影响因子：
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通讯作者：
E. Sikorski;T. Hock;N. Hill-Kapturczak;A. Agarwal
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文献类型：
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作者：
E. Sikorski;T. Hock;N. Hill-Kapturczak;A. Agarwal
血红素加氧酶（HO）催化血红素降解中的限速步骤，导致铁、一氧化碳和胆绿素的形成，后者随后通过胆绿素还原酶转化为胆红素。最近的注意力集中在这种酶促反应的产物的生物学效应上，其具有重要的抗氧化、抗炎和细胞保护功能。已经描述了HO酶的两种主要同种型：诱导型同种型HO-1和组成型表达的同种型HO-2。与HO-2密切相关的第三种亚型HO-3也已被描述。与肾损伤的发病机制有关的几种刺激物，如血红素、一氧化氮、生长因子、血管紧张素II、细胞因子和肾毒素，诱导HO-1。HO-1的诱导作为对这些刺激的适应性和有益的反应而发生，如在肾脏和非肾脏疾病状态中的研究所证明的。本文将重点介绍HO-1基因在肾损伤中的分子调控，并将突出物种间的差异，主要是啮齿动物和人类HO-1基因之间的差异。
Heme oxygenases (HOs) catalyze the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide, and biliverdin, the latter of which is subsequently converted to bilirubin by biliverdin reductase. Recent attention has focused on the biological effects of product(s) of this enzymatic reaction, which have important antioxidant, anti-inflammatory, and cytoprotective functions. Two major isoforms of the HO enzyme have been described: an inducible isoform, HO-1, and a constitutively expressed isoform, HO-2. A third isoform, HO-3, closely related to HO-2, has also been described. Several stimuli implicated in the pathogenesis of renal injury, such as heme, nitric oxide, growth factors, angiotensin II, cytokines, and nephrotoxins, induce HO-1. Induction of HO-1 occurs as an adaptive and beneficial response to these stimuli, as demonstrated by studies in renal and non-renal disease states. This review will focus on the molecular regulation of the HO-1 gene in renal injury and will highlight the interspecies differences, predominantly between the rodent and human HO-1 genes.