Gene regulation of heme oxygenase-1 as a therapeutic target
Gene regulation of heme oxygenase-1 as a therapeutic target
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DOI：
10.1016/s0006-2952(00)00443-3
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发表时间：
2000-10-15
影响因子：
5.8
通讯作者：
Ramadori, G
中科院分区：
文献类型：
--
作者：
Immenschuh, S;Ramadori, G
血红素加氧酶(HO)-1是血红素降解限速酶的诱导亚型。HO调节细胞中促氧化剂血红素的含量，并产生具有生理功能的分解代谢产物。HO-1是由一系列氧化应激刺激诱导的，HO-1基因表达的激活被认为是细胞对环境应激生存的适应性反应。由于HO-1基因的过度表达也对实验性损伤的有害影响具有保护作用，因此“非应激”刺激对HO-1的特异性诱导。与氧化应激无关的刺激物，如3‘，5’-环磷酸腺苷或环鸟苷3‘，5’-单磷酸，可能具有重要的临床意义。本文综述了HO-1基因表达调控机制的最新研究进展，特别是各种氧化还原依赖和非氧化还原信号转导途径的作用。重点介绍了实验性损伤的模型，在这些模型中，通过靶向基因转移或通过药物调节的HO-1基因的特定过度表达已被证明具有治疗效果。Biochem Pharmacol 60；8：1121-1128,2000。(C)2000年爱思唯尔科学公司。
Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation. HO regulates the cellular content of the pro-oxidant heme and produces catabolites with physiological functions. HO-1 is induced by a host of oxidative stress stimuli, and the activation of HO-1 gene expression is considered to be an adaptive cellular response to survive exposure to environmental stresses. Since overexpression of the HO-1 gene is also protective against the deleterious effects of experimental injuries, the specific induction of HO-1 by 'non-stressful' stimuli, eg. stimuli that are not associated with oxidative stress, such as adenosine 3',5'-cyclic monophosphate or cyclic guanosine 3',5'-monophosphate, may have important clinical implications. This review summarizes recent advances in the understanding of regulatory mechanisms of HO-1 gene expression, in particular the role of various redox-dependent and redox-independent signaling pathways. Models of experimental injuries are highlighted in which specific overexpression of the HO-1 gene either by targeted gene transfer or by pharmacological modulation has been demonstrated to provide therapeutic effects. BIOCHEM PHARMACOL 60;8:1121-1128, 2000. (C) 2000 Elsevier Science Inc.