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天然产物在化学预防中的分子机制:Nrf2诱导细胞保护酶

Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2.

作者信息

Eggler Aimee L, Gay Kelly A, Mesecar Andrew D

机构信息

The Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.

出版信息

Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S84-94. doi: 10.1002/mnfr.200700249.

Abstract

Cancer chemoprevention involves the use of natural or synthetic compounds to reduce the risk of developing cancer. One of the potential strategies for preventing cancer in the human population is to use food-based natural products to induce cytoprotective enzymes, such as NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase, superoxide dismutase, and heme oxygenase-1. The regulatory regions of these inducible genes contain the antioxidant response element (ARE), which is activated upon binding of the nuclear factor E2-related protein 2 (Nrf2) transcription factor protein. Nrf2 has been shown to be essential in the upregulation of these genes in response to oxidative stress and treatment with certain dietary phytochemicals. This review presents the current body of knowledge regarding the molecular mechanisms of Nrf2 regulation, and highlights the need for future investigations into how these mechanisms apply to natural product inducers of cytoprotective enzymes.

摘要

癌症化学预防涉及使用天然或合成化合物来降低患癌风险。在人群中预防癌症的一种潜在策略是使用基于食物的天然产物来诱导细胞保护酶,如NAD(P)H:醌氧化还原酶1、谷胱甘肽S-转移酶、超氧化物歧化酶和血红素加氧酶-1。这些可诱导基因的调控区域包含抗氧化反应元件(ARE),它在核因子E2相关蛋白2(Nrf2)转录因子蛋白结合后被激活。已证明Nrf2在响应氧化应激和某些膳食植物化学物质处理时对这些基因的上调至关重要。本综述介绍了关于Nrf2调控分子机制的当前知识体系,并强调了未来需要研究这些机制如何应用于细胞保护酶的天然产物诱导剂。

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