Alam Jawed, Cook Julia L
Department of Molecular Genetics, Ochsner Medical Center, New Orleans, LA 70121, USA.
Am J Respir Cell Mol Biol. 2007 Feb;36(2):166-74. doi: 10.1165/rcmb.2006-0340TR. Epub 2006 Sep 21.
The ability to communicate with the environment and respond to changes--particularly those of an adverse nature--within that environment is critical for cell function and survival. A key component of the overall cellular stress response includes adjustments in the gene expression program in favor of proteins that manifest activities capable of frustrating and eventually eliminating the molecular constituents of the stress condition. One protein providing such cytoprotective activity is heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting reaction in heme catabolism (i.e., the oxidative cleavage of b-type heme molecules to yield equimolar quantities of biliverdin IXalpha, carbon monoxide, and iron). Because of the potent antioxidant, anti-inflammatory, and signaling properties of the reaction products, the HO-1 gene (hmox1) is frequently activated under a variety of cellular stress conditions. Cells use multiple signaling pathways and transcription factors to fine-tune their response to a specific circumstance. Among these factors, members of the heat-shock factor, nuclear factor-kappaB, nuclear factor-erythroid 2, and activator protein-1 families are arguably the most important regulators of the cellular stress response in vertebrates. Although there is functional overlap between individual families, each broadly regulates different aspects of the cellular stress response and thus, with some exceptions, modulates the expression of different sets of targets genes. To the best of our knowledge, hmox1 is unique in that it is proposed to be directly regulated by all four of these stress-responsive transcription factors. In this article we provide a review and analysis of the data supporting this proposition.
与环境进行沟通并对该环境中的变化（尤其是不良性质的变化）做出反应的能力对于细胞功能和存活至关重要。细胞整体应激反应的一个关键组成部分包括基因表达程序的调整，以利于那些表现出能够挫败并最终消除应激条件分子成分活性的蛋白质。一种具有这种细胞保护活性的蛋白质是血红素加氧酶-1（HO-1），它是一种催化血红素分解代谢限速反应（即b型血红素分子的氧化裂解，产生等摩尔量的胆绿素IXα、一氧化碳和铁）的酶。由于反应产物具有强大的抗氧化、抗炎和信号传导特性，HO-1基因（hmox1）在多种细胞应激条件下经常被激活。细胞利用多种信号通路和转录因子来微调其对特定情况的反应。在这些因子中，热休克因子、核因子-κB、核因子-红细胞2和激活蛋白-1家族的成员可以说是脊椎动物细胞应激反应中最重要的调节因子。虽然各个家族之间存在功能重叠，但每个家族广泛调节细胞应激反应的不同方面，因此，除了一些例外情况，调节不同组靶基因的表达。据我们所知，hmox1的独特之处在于它被认为直接受所有这四种应激反应转录因子的调节。在本文中，我们对支持这一观点的数据进行了综述和分析。
