Nrf2, a multi-organ protector?
Nrf2, a multi-organ protector?
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DOI：
10.1096/fj.04-2591hyp
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Johnson, JA
中科院分区：
文献类型：
--
作者：
Lee, JM;Li, J;Johnson, JA
NF-E2 相关因子 2 (Nrf2) 是一种碱性亮氨酸拉链转录因子，与启动子序列“抗氧化反应元件 (ARE)”结合，导致 ARE 驱动的解毒和抗氧化基因协调上调。由于多种抗氧化和解毒基因的表达受到 ARE 序列的正向调节，因此 Nrf2 可以作为 ARE 驱动的细胞防御系统对抗氧化应激的主要调节因子。为了支持这一点，大量研究表明 Nrf2 可以保护许多细胞类型和器官系统免受广泛的毒性损伤和疾病发病机制的影响。这种 Nrf2 赋予的多器官保护现象提出了一个有趣的问题：单一蛋白质如何保护许多不同的器官免受各种毒性侵害。解释这种现象的一个可能的分子机制是，Nrf2 通过协调上调经典的 ARE 驱动基因以及细胞类型特异性靶基因来保护许多不同的细胞类型，这些基因是每种细胞类型在其独特环境中的防御系统所需的。这一假设得到了微阵列数据的支持，表明 Nrf2 的保护作用是通过已知的 ARE 驱动基因和新的细胞类型特异性基因传递的。 Nrf2 的广泛性可能具有重要的治疗潜力，可以预防癌变和神经退行性疾病。
NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that binds to the promoter sequence "antioxidant responsive element (ARE)" leading to coordinated up-regulation of ARE-driven detoxification and antioxidant genes. Since the expression of a wide array of antioxidant and detoxification genes are positively regulated by the ARE sequence, Nrf2 may serve as a master regulator of the ARE-driven cellular defense system against oxidative stress. In support of this, numerous studies have shown that Nrf2 protects many cell types and organ systems from a broad spectrum of toxic insults and disease pathogenesis. This Nrf2-conferred, multi-organ protection phenomenon raises an interesting question about how a single protein can protect many different organs from various toxic insults. A possible molecular mechanism explaining this phenomenon is that Nrf2 protects many different cell types by coordinately up-regulating classic ARE-driven genes as well as cell type-specific target genes that are required for the defense system of each cell type in its unique environment. This hypothesis is supported by microarray data indicating the protective role of Nrf2 is conveyed through both known ARE-driven genes and novel cell type-specific genes. The widespread nature of Nrf2 may have an important therapeutic potential, allowing prevention of carcinogenesis and neurodegenerative diseases.