کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9908964 | 1548427 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nrf2 as a target for cancer chemoprevention
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chemical insults, whether of endogenous or exogenous origins, play major roles in the etiopathogenesis of many cancers. As such, strategies to blunt their formation and limit their damage to biomolecules are a central aspect of chemoprevention. Cellular defenses against such insults are regulated in part by the transcription factor Nrf2. Nrf2, in turn, regulates gene expression through interactions with the ARE (antioxidant-response-element) found in the promoter regions of many cytoprotective genes. Under basal conditions, Nrf2 is tethered in the cytoplasm to an actin binding protein Keap1. Pharmacological and food-derived agents such as dithiolethiones and isothiocyanates trigger the release of Nrf2 from Keap1, allowing it to translocate into the nucleus and stimulate gene transcription. Studies using nrf2-deficient mice have revealed that Nrf2 regulates basal and inducible expression of multiple categories of genes, including xenobiotic-metabolizing enzymes, antioxidant enzymes, molecular chaperones/stress response proteins, as well as proteasome subunits, that collectively reflect the complex and important role Nrf2 plays in the cellular defense against carcinogens. Nrf2 knockout mice are greatly predisposed to chemical-induced DNA damage and exhibit higher susceptibility towards cancer development in several models of chemical carcinogenesis. Nrf2 also mediates protection against oxidative stress and influences inflammatory processes, both of which contribute to carcinogenesis. Observations that nrf2-deficient mice are refractory to the protective actions of some chemopreventive agents highlight the importance of the Keap1-Nrf2-ARE signaling pathway as a molecular target for prevention.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 591, Issues 1â2, 11 December 2005, Pages 93-102
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 591, Issues 1â2, 11 December 2005, Pages 93-102
نویسندگان
Xiang Yu, Thomas Kensler,