WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
the 24th letter of the Roman alphabet (同)x, ex

PrepTutorEJDIC

=sense organ / 受信装置
Christ / Christian
x-axis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/09 12:34:02」(JST)

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"PXR" redirects here. For information on the file format .pxr, see Pixar Image Computer.

In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 gene.^[2]^[3]^[4]^[5]

PXR is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the detoxification and clearance of these substances from the body.^[6] PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized.^[5]^[7]

Activation

PXR is activated by a large number of endogenous and exogenous chemicals including steroids, antibiotics, antimycotics, bile acids, hyperforin, a constituent of the herbal antidepressant St. John's Wort, and many other herbal compounds.^[6]

Function

Like other type II nuclear receptors, when activated, it forms a heterodimer with the retinoid X receptor, and binds to hormone response elements on DNA which elicits expression of gene products.^[6]

One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is responsible for the metabolism of many drugs.^[4]^[5] In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase^[8] and phase III transport uptake and efflux proteins such as OATP2 (SLCO2A1)^[9] and MDR1 (ABCB1).^[10]^[11]

References

^ Liao, S. K.; Axelrad, A. A. (1975). "Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus". International journal of cancer. Journal international du cancer 15 (3): 467–482. PMID 1140862. edit
^ This is the official name, from Nuclear Receptor subfamily 1, group I, member 2.
^ Entrez result for NR1I2.
^ ^a ^b Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (September 1998). "The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions". J. Clin. Invest. 102 (5): 1016–23. doi:10.1172/JCI3703. PMC 508967. PMID 9727070.
^ ^a ^b ^c Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Bäckman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A (October 1998). "Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12208–13. doi:10.1073/pnas.95.21.12208. PMC 22810. PMID 9770465.
^ ^a ^b ^c Kliewer S, Goodwin B, Willson T (2002). "The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism". Endocr. Rev. 23 (5): 687–702. doi:10.1210/er.2001-0038. PMID 12372848.
^ "Entrez Gene: NR1I2 nuclear receptor subfamily 1, group I, member 2".
^ Falkner KC, Pinaire JA, Xiao GH, Geoghegan TE, Prough RA (September 2001). "Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors". Mol. Pharmacol. 60 (3): 611–9. PMID 11502894.
^ Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA (March 2001). "The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3369–74. doi:10.1073/pnas.051551698. PMC 30660. PMID 11248085.
^ Synold TW, Dussault I, Forman BM (May 2001). "The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux". Nat. Med. 7 (5): 584–90. doi:10.1038/87912. PMID 11329060.
^ Geick A, Eichelbaum M, Burk O (May 2001). "Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin". J. Biol. Chem. 276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID 11297522.

External links

pregnane X receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on chromosome 3 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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1. 急性前骨髄球性白血病の分子生物学 molecular biology of acute promyelocytic leukemia
2. 分化（レチノイン酸）症候群 differentiation retinoic acid syndrome
3. 甲状腺ホルモンの作用 thyroid hormone action
4. 中枢性甲状腺機能低下症 central hypothyroidism
5. 甲状腺ホルモンとの薬物相互作用 drug interactions with thyroid hormones

English Journal

Menthol reduces the anticoagulant effect of warfarin by inducing cytochrome P450 2C expression.

Hoshino M1, Ikarashi N1, Tsukui M1, Kurokawa A1, Naito R1, Suzuki M1, Yokobori K1, Ochiai T1, Ishii M1, Kusunoki Y1, Kon R1, Ochiai W1, Wakui N2, Machida Y2, Sugiyama K3.Author information 1Department of Clinical Pharmacokinetics, Hoshi University, Japan.2Division of Applied Pharmaceutical Education and Research, Hoshi University, Japan.3Department of Clinical Pharmacokinetics, Hoshi University, Japan. Electronic address: sugiyama@hoshi.ac.jp.AbstractRecently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Jun 2;56:92-101. doi: 10.1016/j.ejps.2014.02.011. Epub 2014 Mar 1.
Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally admini
PMID 24594507

Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest.

Niu Y1, Wang Z2, Huang H3, Zhong S4, Cai W1, Xie Y5, Shi G6.Author information 1Department of Pharmacology, Shantou University Medical College, Guangdong, China.2Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University, Shanghai, China.3Department of Pathology, Second Affiliated Hospital of Shantou University Medical College, Guangdong, China.4Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.5Department of Experimental Animal Center, Medical College of Shantou University, Guangdong, China.6Department of Pharmacology, Shantou University Medical College, Guangdong, China. Electronic address: ggshi@stu.edu.cn.AbstractPregnane X receptor (PXR) regulates cell proliferation and carcinogenesis in female reproductive tissue. We showed that PXR was expressed in cervical cells and tissue samples. PXR were lower or greatly diminished in cancer tissues compared to normal control. Functionally, activation of human PXR by rifampicin or ectopic expression of constitutively-activated human VP-PXR inhibited cervical cell proliferation. Constitutively-activated VP-PXR attenuated CaSki and HeLa xenograft tumor growth in nude mice compared with control. The cellular proliferation inhibition of PXR by causing G2/M cell-cycle arrest is involved up-regulation of Cullin1-3, MAD2L1, and down-regulation of ANAPC2 and CDKN1A. Our data suggests that PXR signaling inhibits tumor cell proliferation in vitro and cervical carcinoma growth in vivo.
Cancer letters.Cancer Lett.2014 May 28;347(1):88-97. doi: 10.1016/j.canlet.2014.01.026. Epub 2014 Jan 31.
Pregnane X receptor (PXR) regulates cell proliferation and carcinogenesis in female reproductive tissue. We showed that PXR was expressed in cervical cells and tissue samples. PXR were lower or greatly diminished in cancer tissues compared to normal control. Functionally, activation of human PXR by
PMID 24486740

Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis.

Terc J1, Hansen A1, Alston L1, Hirota SA2.Author information 1Departments of Physiology & Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada; Microbiology, Immunology & Infectious Diseases, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada.2Departments of Physiology & Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada; Microbiology, Immunology & Infectious Diseases, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada. Electronic address: simon.hirota@ucalgary.ca.AbstractThe intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis. It is thought that the increased permeability in patients with IBD may be driven by alterations in the epithelial wound healing response. To this end considerable study has been undertaken to identify signaling pathways that may accelerate intestinal epithelial wound healing and normalize the barrier dysfunction observed in IBD. In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response. Mutations and reduced mucosal expression of the PXR are associated with IBD, and others have reported that PXR agonists can dampen intestinal inflammation. Furthermore, stimulation of the PXR has been associated with increased cell migration and proliferation, two of the key processes involved in wound healing. We hypothesized that PXR agonists would enhance intestinal epithelial repair. Stimulation of Caco-2 intestinal epithelial cells with rifaximin, rifampicin and SR12813, all potent agonists of the PXR, significantly increased wound closure. This effect was driven by p38 MAP kinase-dependent cell migration, and occurred in the absence of cell proliferation. Treating mice with a rodent specific PXR agonist, pregnenolone 16α-carbonitrile (PCN), attenuated the intestinal barrier dysfunction observed in the dextran sulphate sodium (DSS) model of experimental colitis, an effect that occurred independent of the known anti-inflammatory effects of PCN. Taken together our data indicate that the activation of the PXR can enhance intestinal epithelial repair and suggest that targeting the PXR may help to normalize intestinal barrier dysfunction observed in patients with IBD. Furthermore, our data provide additional insight into the potential mechanisms through which rifaximin elicits its clinical efficacy in the treatment of IBD.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 May 13;55:12-9. doi: 10.1016/j.ejps.2014.01.007. Epub 2014 Jan 29.
The intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's
PMID 24486481

Japanese Journal

Resveratrol Suppresses the Inducible Expression of CYP3A4 Through the Pregnane X Receptor

Deng Rongrong,Xu Chenshu,Chen Xiao [他]
Journal of pharmacological sciences 126(2), 146-154, 2014-10
NAID 40020237640

ビタミンKと骨代謝(<特集>第65回大会シンポジウム「臨床とビタミンUp-Date」)

柴祥子,井上聡
ビタミン 88(1), 18-24, 2014-01-25
… On the other hand, VK_2 also regulates the transcription of bone-related genes in osteoblasts through activating steroid X receptor (SXR)/pregnane X receptor (PXR), as well as enhancing the phosphorylation of protein kinase A (PKA). …
NAID 110009767428

Roles of Xenobiotic Receptors in Vascular Pathophysiology

, ,
Circulation Journal 78(7), 1520-1530, 2014
… The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcription factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. …
NAID 130004926969

「プレグナン受容体」

Nuclear receptor subfamily 1, group I, member 2
	; PDB rendering based on PDB 1ilg.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1ILG, 1ILH, 1M13, 1NRL, 1SKX, 2O9I, 2QNV, 3CTB, 3HVL, 3R8D
Identifiers
Symbols	NR1I2; BXR; ONR1; PAR; PAR1; PAR2; PARq; PRR; PXR; SAR; SXR
External IDs	OMIM: 603065 MGI: 1337040 HomoloGene: 40757 IUPHAR: NR1I2 ChEMBL: 3401 GeneCards: NR1I2 Gene
Gene Ontology
Molecular function	• steroid hormone receptor activity; • transcription coactivator activity; • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; • protein binding; • drug binding; • zinc ion binding; • sequence-specific DNA binding; • metal ion binding;
Cellular component	• nucleoplasm;
Biological process	• transcription initiation from RNA polymerase II promoter; • xenobiotic metabolic process; • signal transduction; • steroid metabolic process; • gene expression; • intracellular receptor mediated signaling pathway; • exogenous drug catabolic process; • xenobiotic transport; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • drug export;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: pregnane X receptor, PXR

「X」

　　[★] キサントシン, xanthosine 　　

[1] Liao, S. K.; Axelrad, A. A. (1975). "Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus". International journal of cancer. Journal international du cancer 15 (3): 467–482. PMID 1140862. edit

[2] This is the official name, from Nuclear Receptor subfamily 1, group I, member 2.

[3] Entrez result for NR1I2.

[pmid9727070-4] Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (September 1998). "The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions". J. Clin. Invest. 102 (5): 1016–23. doi:10.1172/JCI3703. PMC 508967. PMID 9727070.

[pmid9770465-5] Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Bäckman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A (October 1998). "Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12208–13. doi:10.1073/pnas.95.21.12208. PMC 22810. PMID 9770465.

[Kliewer-6] Kliewer S, Goodwin B, Willson T (2002). "The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism". Endocr. Rev. 23 (5): 687–702. doi:10.1210/er.2001-0038. PMID 12372848.

[entrez-7] "Entrez Gene: NR1I2 nuclear receptor subfamily 1, group I, member 2".

[pmid11502894-8] Falkner KC, Pinaire JA, Xiao GH, Geoghegan TE, Prough RA (September 2001). "Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors". Mol. Pharmacol. 60 (3): 611–9. PMID 11502894.

[pmid11248085-9] Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA (March 2001). "The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3369–74. doi:10.1073/pnas.051551698. PMC 30660. PMID 11248085.

[pmid11329060-10] Synold TW, Dussault I, Forman BM (May 2001). "The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux". Nat. Med. 7 (5): 584–90. doi:10.1038/87912. PMID 11329060.

[pmid11297522-11] Geick A, Eichelbaum M, Burk O (May 2001). "Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin". J. Biol. Chem. 276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID 11297522.

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pregnane X receptor