Transactivation of Genes Encoding for Phase II Enzymes and Phase III Transporters by Phytochemical Antioxidants 英文参考文献.docVIP

Molecules 2010, 15, 6332-6348; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Transactivation of Genes Encoding for Phase II Enzymes and Phase III Transporters by Phytochemical Antioxidants Yoon Mee Yang, Kyoung Noh, Chang Yeob Han and Sang Geon Kim * Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy, Seoul National University, Gwanak-ro 599, Seoul 151-742, Korea * Author to whom correspondence should be addressed; E-Mail: sgk@snu.ac.kr; Tel.: +82-2-880-7840; Fax: +82-2-872-1795. Received: 6 August 2010; in revised form: 31 August 2010 / Accepted: 3 September 2010 / Published: 7 September 2010 Abstract: The induction of phase II enzymes and phase III transporters contributes to the metabolism, detoxification of xenobiotics, antioxidant capacity, redox homeostasis and cell viability. Transactivation of the genes that encode for phase II enzymes and phase III transporters is coordinatively regulated by activating transcription factors in response to external stimuli. Comprehensive studies indicate that antioxidant phytochemicals promote the induction of phase II enzymes and/or phase III transporters through various signaling pathways, including phosphoinositide 3-kinase, protein kinase C, and mitogen-activated protein kinases. This paper focuses on the molecular mechanisms and signaling pathways responsible for the transactivation of genes encoding for these proteins, as orchestrated by a series of transcription factors and related signaling components. Keywords: phase 2 enzyme; phase 3 transporter; NF-E2-related factor 2; CCAAT- enhancer binding protein-β; hepatic nuclear factor; farnesoid X receptor 1. Introduction Biotransformation of xenobiotics including drugs is catalyzed by enzymes which are commonly referred to as drug-metabolizing enzymes. Most tissues and organs have detoxifying systems