The Roles of Xenobiotic Receptors: Beyond Chemical Disposition

Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous and exogenous stimuli has been extensively characterized and well documented. The constitutive androstane receptor (CAR) and the pregnane X r...

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Published inDrug metabolism and disposition Vol. 46; no. 9; pp. 1361 - 1371
Main Authors Mackowiak, Bryan, Hodge, Jessica, Stern, Sydney, Wang, Hongbing
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.09.2018
American Society for Pharmacology and Experimental Therapeutics, Inc
The American Society for Pharmacology and Experimental Therapeutics
Subjects
Animals
Cancer
Cell Proliferation
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Constitutive Androstane Receptor
Drug metabolism
Energy balance
Energy Metabolism
Gene Expression Regulation, Neoplastic
Homeostasis
Humans
Immune clearance
Immune response
Immune system
Metabolism
Minireview
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Organic chemistry
Pregnane X Receptor - genetics
Pregnane X Receptor - metabolism
Proteins
Receptors
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Signal Transduction
Xenobiotics - metabolism
T4
NR
PEPCK
PGC1α
EGF
HFD
HCC
PXR
RXR
PB
G6Pase
CAR
miRNA
TCPOBOP
PCN
XR
DME
SGK2
WT
T3
Online AccessGet full text

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Abstract Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous and exogenous stimuli has been extensively characterized and well documented. The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are the xenobiotic receptors that have received the most attention since they regulate the expression of numerous proteins important to drug metabolism and clearance and formulate a central defensive mechanism to protect the body against xenobiotic challenges. However, accumulating evidence has shown that these xenobiotic sensors also control many cellular processes outside of their traditional realms of xenobiotic metabolism and disposition, including physiologic and/or pathophysiologic responses in energy homeostasis, cell proliferation, inflammation, tissue injury and repair, immune response, and cancer development. This review will highlight recent advances in studying the noncanonical functions of xenobiotic receptors with a particular focus placed on the roles of CAR and PXR in energy homeostasis and cancer development.
AbstractList Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous and exogenous stimuli has been extensively characterized and well documented. The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are the xenobiotic receptors that have received the most attention since they regulate the expression of numerous proteins important to drug metabolism and clearance and formulate a central defensive mechanism to protect the body against xenobiotic challenges. However, accumulating evidence has shown that these xenobiotic sensors also control many cellular processes outside of their traditional realms of xenobiotic metabolism and disposition, including physiologic and/or pathophysiologic responses in energy homeostasis, cell proliferation, inflammation, tissue injury and repair, immune response, and cancer development. This review will highlight recent advances in studying the noncanonical functions of xenobiotic receptors with a particular focus placed on the roles of CAR and PXR in energy homeostasis and cancer development.
Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous and exogenous stimuli has been extensively characterized and well documented. The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are the xenobiotic receptors that have received the most attention since they regulate the expression of numerous proteins important to drug metabolism and clearance and formulate a central defensive mechanism to protect the body against xenobiotic challenges. However, accumulating evidence has shown that these xenobiotic sensors also control many cellular processes outside of their traditional realms of xenobiotic metabolism and disposition, including physiologic and/or pathophysiologic responses in energy homeostasis, cell proliferation, inflammation, tissue injury and repair, immune response, and cancer development. This review will highlight recent advances in studying the noncanonical functions of xenobiotic receptors with a particular focus placed on the roles of CAR and PXR in energy homeostasis and cancer development.Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous and exogenous stimuli has been extensively characterized and well documented. The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are the xenobiotic receptors that have received the most attention since they regulate the expression of numerous proteins important to drug metabolism and clearance and formulate a central defensive mechanism to protect the body against xenobiotic challenges. However, accumulating evidence has shown that these xenobiotic sensors also control many cellular processes outside of their traditional realms of xenobiotic metabolism and disposition, including physiologic and/or pathophysiologic responses in energy homeostasis, cell proliferation, inflammation, tissue injury and repair, immune response, and cancer development. This review will highlight recent advances in studying the noncanonical functions of xenobiotic receptors with a particular focus placed on the roles of CAR and PXR in energy homeostasis and cancer development.
Author Hodge, Jessica
Mackowiak, Bryan
Wang, Hongbing
Stern, Sydney
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Copyright 2018 American Society for Pharmacology and Experimental Therapeutics
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NR
PEPCK
PGC1α
EGF
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HCC
PXR
RXR
PB
G6Pase
CAR
miRNA
TCPOBOP
PCN
XR
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Snippet Over the past 20 years, the ability of the xenobiotic receptors to coordinate an array of drug-metabolizing enzymes and transporters in response to endogenous...
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pubmed
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SubjectTerms Animals
Cancer
Cell Proliferation
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Constitutive Androstane Receptor
Drug metabolism
Energy balance
Energy Metabolism
Gene Expression Regulation, Neoplastic
Homeostasis
Humans
Immune clearance
Immune response
Immune system
Metabolism
Minireview
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Organic chemistry
Pregnane X Receptor - genetics
Pregnane X Receptor - metabolism
Proteins
Receptors
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Signal Transduction
Xenobiotics - metabolism
Title The Roles of Xenobiotic Receptors: Beyond Chemical Disposition
URI https://dx.doi.org/10.1124/dmd.118.081042
https://www.ncbi.nlm.nih.gov/pubmed/29759961
https://www.proquest.com/docview/2164526800
https://www.proquest.com/docview/2039292332
https://pubmed.ncbi.nlm.nih.gov/PMC6124513
Volume 46
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