Homeostatic control of xeno- and endobiotics in the drug-metabolizing enzyme system

被引:38
作者
Bock, Karl Walter [1 ]
机构
[1] Univ Tubingen, Inst Expt & Clin Pharmacol & Toxicol, Dept Toxicol, D-72074 Tubingen, Germany
关键词
CYP1; UGT1; Ah receptor; FICZ; Bilirubin; Phytochemicals; ARYL-HYDROCARBON RECEPTOR; PREGNANE-X-RECEPTOR; PHENOL UDP-GLUCURONOSYLTRANSFERASES; CONSTITUTIVE ANDROSTANE RECEPTOR; AH RECEPTOR; NUCLEAR RECEPTORS; TRANSCRIPTIONAL REGULATION; MEDIATED INDUCTION; DIOXIN RECEPTOR; CYP1A2; GENES;
D O I
10.1016/j.bcp.2014.04.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Drug-metabolizing Phase I and II enzyme families, drug transporters (Phase III) and their ligandactivated transcription factors probably evolved as a system involved in homeostatic control of lipophilic endobiotics and detoxification of xenobiotics. The review is focused on CYP, UGT enzymes and the Ah receptor as transcription factor. The hypothesis of a system is supported by (i) coordinate regulation of subsets of these enzyme families and transporters by transcription factors including the AhR, and (ii) feedback loops between endobiotic AhR agonists and substrates of major catabolic target genes/proteins; for example, 6-formylindolo[3,2-blcarbazole as substrate of CYP1A1, and bilirubin, as substrate of UGT1A1. In the latter case the AhR is one of multiple transcription factors contributing to bilirubin homeostasis. Interestingly, xenobiotics including dietary phytochemicals, products of microbiota, ubiquitous environmental pollutants such as benzo[a]pyrene may also have shaped this system in intestinal epithelia during millions of years of evolution. Most lipophilic drugs are metabolized by the same system since drug-metabolizing enzymes are broad substrate spectrum enzymes. Better understanding of this system may lead to generation of drugs with desirable therapeutic properties. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:1 / 6
页数:6
相关论文
共 83 条
[71]   Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo [J].
Terao, Junji ;
Murota, Kaeko ;
Kawai, Yoshichika .
FOOD & FUNCTION, 2011, 2 (01) :11-17
[72]   The Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes Human Plasmacytoid and Myeloid Dendritic Cell Development from CD34+ Hematopoietic Progenitor Cells [J].
Thordardottir, Soley ;
Hangalapura, Basav N. ;
Hutten, Tim ;
Cossu, Marta ;
Spanholtz, Jan ;
Schaap, Nicolaas ;
Radstake, Timothy R. D. J. ;
van der Voort, Robbert ;
Dolstra, Harry .
STEM CELLS AND DEVELOPMENT, 2014, 23 (09) :955-967
[73]  
Togawa Hiroshi, 2008, Drug Metab Lett, V2, P231, DOI 10.2174/187231208786734120
[74]   A novel xenobiotic responsive element regulated by aryl hydrocarbon receptor is involved in the induction of BCRP/ABCG2 in LS174T cells [J].
Tompkins, Leslie M. ;
Li, Haishan ;
Li, Linhao ;
Lynch, Caitlin ;
Xie, Yi ;
Nakanishi, Takeo ;
Ross, Douglas D. ;
Wang, Hongbing .
BIOCHEMICAL PHARMACOLOGY, 2010, 80 (11) :1754-1761
[75]   A common regulatory region functions bidirectionally in transcriptional activation of the human CYP1A1 and CYP1A2 genes [J].
Ueda, Rika ;
Iketaki, Hiromi ;
Nagata, Kiyoshi ;
Kimura, Shioko ;
Gonzalez, Frank J. ;
Kusano, Kazutomi ;
Yoshimura, Tsutomu ;
Yamazoe, Yasushi .
MOLECULAR PHARMACOLOGY, 2006, 69 (06) :1924-1930
[76]  
Vasiliou Vasilis, 2009, Human Genomics, V3, P281
[77]   Cross-talk between Aryl Hydrocarbon Receptor and the Inflammatory Response A ROLE FOR NUCLEAR FACTOR-κB [J].
Vogel, Christoph F. A. ;
Khan, Elaine M. ;
Leung, Patrick S. C. ;
Gershwin, M. Eric ;
Chang, W. L. William ;
Wu, Dalei ;
Haarmann-Stemmann, Thomas ;
Hoffmann, Alexander ;
Denison, Michael S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (03) :1866-1875
[78]   Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation [J].
Vogel, Christoph F. A. ;
Wu, Dalei ;
Goth, Samuel R. ;
Baek, Jaeeun ;
Lollies, Anna ;
Domhardt, Rowena ;
Grindel, Annemarie ;
Pessah, Isaac N. .
IMMUNOLOGY AND CELL BIOLOGY, 2013, 91 (09) :568-575
[79]   Differential Consequences of Two Distinct AhR Ligands on Innate and Adaptive Immune Responses to Influenza A Virus [J].
Wheeler, Jennifer L. H. ;
Martin, Kyle C. ;
Resseguie, Emily ;
Lawrence, B. Paige .
TOXICOLOGICAL SCIENCES, 2014, 137 (02) :324-334
[80]   Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor [J].
Wincent, Emma ;
Bengtsson, Johanna ;
Bardbori, Afshin Mohammadi ;
Alsberg, Tomas ;
Luecke, Sandra ;
Rannug, Ulf ;
Rannug, Agneta .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (12) :4479-4484