Activation of coupled Ah receptor and Nrf2 gene batteries by dietary phytochemicals in relation to chemoprevention
Activation of coupled Ah receptor and Nrf2 gene batteries by dietary phytochemicals in relation to chemoprevention
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DOI：
10.1016/j.bcp.2006.04.017
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发表时间：
2006-09-28
影响因子：
5.8
通讯作者：
Bock, Karl Walter
中科院分区：
文献类型：
--
作者：
Koehle, Christoph;Bock, Karl Walter
Ah受体(AhR)是一种配体激活的转录因子，属于bHLH/PAS(Basic Helix-loop-Helix/Per-Arnt-Sim)化学传感器和发育调节剂家族的成员。它代表着一种多功能的分子开关，参与调节内源和外源代谢、血管发育和二恶英介导的毒性。最近，氧化应激保护的Nrf2被证明是AhR的下游靶点[Miao W，Hu L，Scrivens PJ，BATIST G.通过芳烃受体-异种反应元件信号通路转录调控NF-E2 P45调节因子(NRF2)的表达。生物化学杂志2005年第280期：20340-8期)。这一发现提供了一种可能性，即11相异生代谢酶的AhR和Nrf2基因组不同但部分重叠，可以被一些植物化学物质协同激活，作为靶基因的选择性或混合激活剂。此外，可以想象的是，AhR介导的氧化/亲电应激可以通过耦合的Nrf2激活来减弱。该评论讨论了(I)选择性Nrf2和(Ii)植物化学物质协同AhR加Nrf2激活在癌症和退行性疾病的化学预防中的潜力和局限性，并描述了临床试验，提供了对化学预防措施可能有利地调节高危人群不可避免的内源性和外源性毒素暴露的期望。(C)2006 Elsevier Inc.保留所有权利。
The Ah receptor (AhR) is a ligand-activated transcription factor and member of the bHLH/PAS (basic helix-loop-helix/Per-Arnt-Sim) family of chemosensors and developmental regulators. it represents a multifunctional molecular switch involved in regulation of endo- and xenobiotic metabolism, in vascular development and in dioxin-mediated toxicities. Recently, the oxidative stress-protecting Nrf2 has been shown to be a downstream target of the AhR [Miao W, Hu L, Scrivens PJ, Batist G. Transcriptional regulation of NF-E2 p45-regulated factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway. J Biol Chem 2005;280:20340-8). This finding offers the possibility that distinct but partially overlapping AhR and Nrf2 gene batteries of Phase 11 xenobiotic-metabolizing enzymes can be synergistically activated by a number of phytochemicals, acting as selective or mixed activators of target genes. In addition, it is conceivable that AhR-mediated oxidative/electrophile stress may be attenuated by coupled Nrf2 activation. The commentary discusses potentials and limitations of (i) selective Nrf2 and of (ii) synergistic AhR plus Nrf2 activation by phytochemicals in efforts towards chemoprevention of cancer and degenerative diseases, and describes clinical trials providing the expectation that chemopreventive measures may favorably modulate unavoidable endo- and exogenous toxin exposures in high risk populations. (c) 2006 Elsevier Inc. All rights reserved.