Keap1-Nrf2 signaling pathway: Mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles

被引：138

作者：

Turpaev, K. T. ^{[1
]}

机构：

[1] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow 119991, Russia

来源：

BIOCHEMISTRY-MOSCOW | 2013年 / 78卷 / 02期

关键词：

protective genes; xenobiotics; thiols; electrophiles; Keap1; Nrf2; NF-KAPPA-B; ACTIVATED RECEPTOR-GAMMA; PROTEIN S-GUANYLATION; YA-SUBUNIT GENE; NITRIC-OXIDE; OXIDATIVE STRESS; TRANSCRIPTIONAL REGULATION; SYNTHETIC TRITERPENOIDS; CANCER CHEMOPREVENTION; COVALENT MODIFICATION;

D O I：

10.1134/S0006297913020016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The transcription factor Nrf2 governs the expression of a considerable group of genes involved in cell protection against oxidants, electrophiles, and genotoxic compounds. The activity of Nrf2 is sensitive to xenobiotics and endogenous electrophiles. Nrf2 is negatively regulated by specific suppressor protein Keap1, which is also a receptor of electrophiles and adapter for Cul3 ubiquitin ligase. Electrophiles react with critical thiol groups of Keap1 leading to the loss of its ability to inhibit Nrf2. The Keap1-Nrf2 signaling pathway also down-regulates NF-kappa B transcriptional activity and attenuates cytokine-mediated induction of proinflammatory genes. Pharmacological activation of the Keap1-Nrf2 pathway can be used for treatment and prevention of many diseases. Widely known natural Keap1-Nrf2 activators include curcumin, quercetin, resveratrol, and sulforaphane. The most effective Keap1-Nrf2 activators are synthetic oleanane triterpenoids.

引用

页码：111 / 126

页数：16

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