The nuclear receptor PXR: A master regulator of "Homeland" Defense

被引:67
作者
Dussault, I [1 ]
Forman, BM [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Med, Duarte, CA 91010 USA
来源
CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION | 2002年 / 12卷 / 01期
关键词
nuclear receptor; orphan; ligand; bile acid; xenobiotic; metabolism;
D O I
10.1615/CritRevEukaryotGeneExpr.v12.i1.30
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Human beings are constantly exposed to toxic chemicals present in food and the environment. We are also challenged by toxic byproducts of chemical reactions within our own bodies. These toxins need to be inactivated or excreted to maintain homeostasis. Pregnane X receptor (PXR) is a promiscuous nuclear receptor that is activated by a diverse array of endogenous and exogenous toxins. On activation, PXR regulates a number of target genes involved in drug metabolism and efflux in two key target tissues: the liver and intestine. In this article, we review the data accumulated in the last few years identifying PXR as a central player in the integration of these pathways.
引用
收藏
页码:53 / 64
页数:12
相关论文
共 90 条
  • [1] Cytochromes P450 and metabolism of xenobiotics
    Anzenbacher, P
    Anzenbacherová, E
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2001, 58 (5-6) : 737 - 747
  • [2] 6α-hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes
    Araya, Z
    Wikvall, K
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1999, 1438 (01): : 47 - 54
  • [3] BACHS L, 1989, LANCET, V1, P574
  • [4] Drug interaction between St. John's wort and cyclosporine
    Barone, GW
    Gurley, BJ
    Ketel, BL
    Lightfoot, ML
    Abul-Ezz, SR
    [J]. ANNALS OF PHARMACOTHERAPY, 2000, 34 (09) : 1013 - 1016
  • [5] Barwick JL, 1996, MOL PHARMACOL, V50, P10
  • [6] BATTA AK, 1985, J LIPID RES, V26, P690
  • [7] Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery
    Benet, LZ
    Izumi, T
    Zhang, YC
    Silverman, JA
    Wacher, VJ
    [J]. JOURNAL OF CONTROLLED RELEASE, 1999, 62 (1-2) : 25 - 31
  • [8] The novel cholesterol-lowering drug SR-12813 inhibits cholesterol synthesis via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
    Berkhout, TA
    Simon, HM
    Patel, DD
    Bentzen, C
    Niesor, E
    Jackson, B
    Suckling, KE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (24) : 14376 - 14382
  • [9] SR-12813 lowers plasma cholesterol in beagle dogs by decreasing cholesterol biosynthesis
    Berkhout, TA
    Simon, HM
    Jackson, B
    Yates, J
    Pearce, N
    Groot, PHE
    Bentzen, C
    Niesor, E
    Kerns, WD
    Suckling, KE
    [J]. ATHEROSCLEROSIS, 1997, 133 (02) : 203 - 212
  • [10] Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction
    Bertilsson, G
    Heidrich, J
    Svensson, K
    Åsman, M
    Jendeberg, L
    Sydow-Bäckman, M
    Ohlsson, R
    Postlind, H
    Blomquist, P
    Berkenstam, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) : 12208 - 12213