Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism.
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism.
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DOI：
10.1007/s00018-016-2223-0
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Dulak J
中科院分区：
文献类型：
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作者：
Loboda A;Damulewicz M;Pyza E;Jozkowicz A;Dulak J
多功能调节核因子红细胞2相关因子（Nrf 2）不仅被认为是一种细胞保护因子，调节编码抗氧化、抗炎和解毒蛋白的基因的表达，而且也是物种寿命的有力调节剂。脊椎动物Nrf 2属于Cap 'n' Collar（Cnc）bZIP转录因子家族，与秀丽隐杆线虫SKN-1或果蝇CncC具有高度同源性。Nrf 2的主要特征在一定程度上被Nrf 2依赖性基因及其蛋白质模仿，包括血红素加氧酶-1（HO-1），其除了去除有毒血红素之外，还产生胆绿素、铁离子和一氧化碳。HO-1及其产物通过抗氧化损伤、调节细胞凋亡、调节炎症以及促进血管生成发挥有益作用。另一方面，正常HO-1水平的紊乱与一些年龄依赖性疾病的发病机制相关，包括神经变性、癌症或黄斑变性。这篇综述总结了我们对Nrf 2和HO-1跨不同门的知识，表明它们作为应激保护和抗衰老因子的保守作用。
The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. The vertebrate Nrf2 belongs to Cap ‘n’ Collar (Cnc) bZIP family of transcription factors and shares a high homology with SKN-1 from Caenorhabditis elegans or CncC found in Drosophila melanogaster. The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. HO-1 and their products exert beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. On the other hand, the disturbances in the proper HO-1 level are associated with the pathogenesis of some age-dependent disorders, including neurodegeneration, cancer or macular degeneration. This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors.