関: PPAR-alpha、PPARalpha

WordNet

first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
the 1st letter of the Greek alphabet
the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
early testing stage of a software or hardware product; "alpha version"
aerate (sewage) so as to favor the growth of organisms that decompose organic matter (同)aerate
make (substances) radioactive
make active or more active; "activate an old file"
make more adsorptive; "activate a metal"
rendered active; e.g. rendered radioactive or luminescent or photosensitive or conductive
(of e.g. a molecule) made reactive or more reactive (同)excited
(military) set up and placed on active assignment; "a newly activated unit"
(of sewage) treated with aeration and bacteria to aid decomposition
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
any high mountain

PrepTutorEJDIC

アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
…'を'活動的にする / …‘に'放射能を与える / 〈物質〉'を'活性化する
=sense organ / 受信装置
高山,高峰

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/03/22 18:02:15」(JST)

wiki en

Peroxisome proliferator-activated receptor alpha (PPAR-alpha), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein that in humans is encoded by the PPARA gene.^[5] Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.^[6]

Function

Mouse liver PPARalpha transcriptome

Human hepatocyte PPARalpha transcriptome

PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver. PPAR-alpha is activated under conditions of energy deprivation and is necessary for the process of ketogenesis, a key adaptive response to prolonged fasting.^[7] Activation of PPAR-alpha promotes uptake, utilization, and catabolism of fatty acids by upregulation of genes involved in fatty acid transport, fatty acid binding and activation, and peroxisomal and mitochondrial fatty acid β-oxidation.^[8] PPAR-alpha is primarily activated through ligand binding. Synthetic ligands include the fibrate drugs, which are used to treat hyperlipidemia, and a diverse set of insecticides, herbicides, plasticizers, and organic solvents collectively referred to as peroxisome proliferators. Endogenous ligands include fatty acids such as arachidonic acid as well as other polyunsaturated fatty acids and various fatty acid-derived compounds such as certain members of the 15-hydroxyicosatetraenoic acid family of arachidonic acid metabolites, e.g. 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE and 13-hydroxyoctadecadienoic acid, a linoleic acid metabolite.

Tissue distribution

Expression of PPAR-alpha is highest in tissues that oxidize fatty acids at a rapid rate. In rodents, highest mRNA expression levels of PPAR-alpha are found in liver and brown adipose tissue, followed by heart and kidney.^[9] Lower PPAR-alpha expression levels are found in small and large intestine, skeletal muscle and adrenal gland. Human PPAR-alpha seems to be expressed more equally among various tissues, with high expression in liver, intestine, heart, and kidney.

Knock-out studies

Studies using mice lacking functional PPAR-alpha indicate that PPAR-alpha is essential for induction of peroxisome proliferation by a diverse set of synthetic compounds referred to as peroxisome proliferators.^[10] Mice lacking PPAR-alpha also have an impaired response to fasting, characterized by major metabolic perturbations including low plasma levels of ketone bodies, hypoglycemia, and fatty liver.^[7]

Pharmacology

PPAR-alpha serves as cellular receptor for fibrates, a class of drugs used in the treatment of dyslipidemia. Fibrates effectively lower serum triglycerides and raises serum HDL-cholesterol levels.^[11] Although clinical benefits of fibrate treatment have been observed, the overall results are mixed and have led to reservations about the broad application of fibrates for the treatment of coronary heart disease, in contrast to statins. PPAR-alpha agonists may carry therapeutic value for the treatment of non-alcoholic fatty liver disease. PPAR-alpha may also be a site of action of certain anticonvulsants.^[12]^[13]

Target genes

PPAR-alpha governs biological processes by altering the expression of a large number of target genes. Accordingly, the functional role of PPAR-alpha is directly related to the biological function of its target genes. Gene expression profiling studies have indicated that PPAR-alpha target genes number in the hundreds.^[8] Classical target genes of PPAR-alpha include PDK4, ACOX1, and CPT1. Low and high throughput gene expression analysis have allowed the creation of comprehensive maps illustrating the role of PPAR-alpha as master regulator of lipid metabolism via regulation of numerous genes involved in various aspects of lipid metabolism. The maps, constructed for mouse liver and human liver, put PPAR-alpha at the center of a regulatory hub impacting fatty acid uptake and intracellular binding, mitochondrial β-oxidation and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, gluconeogenesis, and bile synthesis/secretion.

Interactions

Peroxisome proliferator-activated receptor alpha has been shown to interact with:

AIP,^[14]
EP300^[15]^[16]
HSP90AA1,^[14]
NCOA1,^[15]^[17] and
NCOR1.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000186951 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022383 - Ensembl, May 2017
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Sher T, Yi HF, McBride OW, Gonzalez FJ (June 1993). "cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor". Biochemistry. 32 (21): 5598–604. doi:10.1021/bi00072a015. PMID 7684926.
^ Issemann I, Green S (October 1990). "Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators". Nature. 347 (6294): 645–54. doi:10.1038/347645a0. PMID 2129546.
^ ^a ^b Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W (June 1999). "Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting". J Clin Invest. 103 (11): 1489–98. doi:10.1172/JCI6223. PMC 408372 . PMID 10359558.
^ ^a ^b Kersten S (2014). "Integrated physiology and systems biology of PPARα". Molecular Metabolism. 3: 354–371. doi:10.1016/j.molmet.2014.02.002. PMC 4060217 . PMID 24944896.
^ Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W (January 1995). "Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat". Endocrinology. 137 (1): 354–66. doi:10.1210/endo.137.1.8536636. PMID 8536636.
^ Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ (June 1995). "Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators". Mol Cell Biol. 15 (6): 3012–22. PMC 230532 . PMID 7539101.
^ Staels B, Maes M, Zambon A (September 2008). "Peroxisome Fibrates and future PPARα agonists in the treatment of cardiovascular disease". Nat Clin Pract Cardiovasc Med. 5 (9): 542–53. doi:10.1038/ncpcardio1278. PMID 18628776.
^ Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, Scheggi S, Carta G, Murru E, Aroni S, Muntoni AL, Pistis M (2013). "PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings". PLoS ONE. 8 (5): e64541. doi:10.1371/journal.pone.0064541. PMC 3664607 . PMID 23724059.
^ Citraro R, Russo E, Scicchitano F, van Rijn CM, Cosco D, Avagliano C, Russo R, D'Agostino G, Petrosino S, Guida F, Gatta L, van Luijtelaar G, Maione S, Di Marzo V, Calignano A, De Sarro G (2013). "Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy". Neuropharmacology. 69: 115–26. doi:10.1016/j.neuropharm.2012.11.017. PMID 23206503.
^ ^a ^b Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH (February 2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID 12482853.
^ ^a ^b Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (December 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". J. Biol. Chem. 272 (52): 33435–43. doi:10.1074/jbc.272.52.33435. PMID 9407140.
^ ^a ^b Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. PMID 10336495.
^ Treuter E, Albrektsen T, Johansson L, Leers J, Gustafsson JA (June 1998). "A regulatory role for RIP140 in nuclear receptor activation". Mol. Endocrinol. 12 (6): 864–81. doi:10.1210/mend.12.6.0123. PMID 9626662.

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「PPAR-alpha」

PPARA
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1I7G, 1K7L, 1KKQ, 2NPA, 2P54, 2REW, 2ZNN, 3ET1, 3FEI, 3G8I, 3KDT, 3KDU, 3SP6, 3VI8, 4BCR, 4CI4, 5AZT
Identifiers
Aliases	PPARA, NR1C1, PPAR, PPARalpha, hPPAR, peroxisome proliferator activated receptor alpha
External IDs	MGI: 104740 HomoloGene: 21047 GeneCards: PPARA
Gene location (Human)
Chr.	Chromosome 22 (human)
End	46,243,756 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	85,802,819 bp
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• NFAT protein binding; • receptor activity; • DNA binding; • sequence-specific DNA binding; • phosphatase binding; • protein domain specific binding; • transcription factor activity, sequence-specific DNA binding; • zinc ion binding; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; • MDM2/MDM4 family protein binding; • metal ion binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding; • transcriptional activator activity, RNA polymerase II transcription factor binding; • steroid hormone receptor activity; • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; • protein binding; • drug binding; • RNA polymerase II repressing transcription factor binding; • transcription coactivator binding; • ubiquitin conjugating enzyme binding; • lipid binding; • transcription factor binding; • RNA polymerase II transcription factor activity, sequence-specific DNA binding;
Cellular component	• Cell nucleus; • nucleoplasm;
Biological process	• lipoprotein metabolic process; • negative regulation of pri-miRNA transcription from RNA polymerase II promoter; • positive regulation of fatty acid beta-oxidation; • negative regulation of glycolytic process; • response to hypoxia; • regulation of transcription, DNA-templated; • negative regulation of blood pressure; • lipid metabolic process; • rhythmic process; • negative regulation of receptor biosynthetic process; • wound healing; • negative regulation of leukocyte cell-cell adhesion; • negative regulation of transcription from RNA polymerase II promoter; • fatty acid transport; • negative regulation of protein binding; • negative regulation of appetite; • circadian regulation of gene expression; • transcription, DNA-templated; • fatty acid metabolic process; • behavioral response to nicotine; • positive regulation of transcription, DNA-templated; • negative regulation of cholesterol storage; • response to insulin; • heart development; • intracellular receptor signaling pathway; • negative regulation of transcription regulatory region DNA binding; • negative regulation of sequestering of triglyceride; • regulation of circadian rhythm; • regulation of fatty acid metabolic process; • epidermis development; • regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter; • regulation of gene expression; • enamel mineralization; • positive regulation of gluconeogenesis; • transcription initiation from RNA polymerase II promoter; • negative regulation of inflammatory response; • negative regulation of macrophage derived foam cell differentiation; • regulation of glycolytic process by positive regulation of transcription from RNA polymerase II promoter; • regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter; • positive regulation of transcription from RNA polymerase II promoter; • steroid hormone mediated signaling pathway; • negative regulation of neuron death; • positive regulation of fatty acid oxidation; • regulation of lipid metabolic process;
	Sources:Amigo / QuickGO
Orthologs
	5465
	19013
	ENSG00000186951
	ENSMUSG00000022383
	Q07869; Q86SF0
	P23204
	NM_001001928; NM_001001929; NM_001001930; NM_005036; NM_032644
	NM_001113418; NM_011144
	NP_001001928; NP_005027
	NP_001106889; NP_035274
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

ペルオキシソーム増殖剤活性化受容体α、ペルオキシソーム増殖因子活性化受容体α、PPARα

関: peroxisome proliferator-activated receptor alpha、PPARalpha

「ペルオキシソーム増殖剤活性化受容体α」

　　[★]

英: peroxisome proliferator-activated receptor alpha、PPAR-alpha
関: ペルオキシソーム増殖因子活性化受容体α、PPAR-α、PPARα

「activated」

　　[★]

adj.

活性化の、活性化型の、賦活化の

関: activate、activated form、activation、turn on

「activate」

　　[★]

v.

活性化する、賦活化する、賦活する

関: activated、activation、turn on

「alpha」

　　[★]

α、アルファ

関: alfa

「peroxisome proliferator」

　　[★]

ペルオキシソーム増殖因子

「proliferator」

　　[★]

増殖因子

関: growth factor

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000186951 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022383 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[pmid7684926-5] Sher T, Yi HF, McBride OW, Gonzalez FJ (June 1993). "cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor". Biochemistry. 32 (21): 5598–604. doi:10.1021/bi00072a015. PMID 7684926.

[pmid2129546-6] Issemann I, Green S (October 1990). "Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators". Nature. 347 (6294): 645–54. doi:10.1038/347645a0. PMID 2129546.

[pmid10359558-7] Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W (June 1999). "Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting". J Clin Invest. 103 (11): 1489–98. doi:10.1172/JCI6223. PMC 408372 . PMID 10359558.

[pmid24944896-8] Kersten S (2014). "Integrated physiology and systems biology of PPARα". Molecular Metabolism. 3: 354–371. doi:10.1016/j.molmet.2014.02.002. PMC 4060217 . PMID 24944896.

[pmid8536636-9] Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W (January 1995). "Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat". Endocrinology. 137 (1): 354–66. doi:10.1210/endo.137.1.8536636. PMID 8536636.

[pmid7539101-10] Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ (June 1995). "Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators". Mol Cell Biol. 15 (6): 3012–22. PMC 230532 . PMID 7539101.

[pmid18628776-11] Staels B, Maes M, Zambon A (September 2008). "Peroxisome Fibrates and future PPARα agonists in the treatment of cardiovascular disease". Nat Clin Pract Cardiovasc Med. 5 (9): 542–53. doi:10.1038/ncpcardio1278. PMID 18628776.

[pmid23724059-12] Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, Scheggi S, Carta G, Murru E, Aroni S, Muntoni AL, Pistis M (2013). "PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings". PLoS ONE. 8 (5): e64541. doi:10.1371/journal.pone.0064541. PMC 3664607 . PMID 23724059.

[pmid23206503-13] Citraro R, Russo E, Scicchitano F, van Rijn CM, Cosco D, Avagliano C, Russo R, D'Agostino G, Petrosino S, Guida F, Gatta L, van Luijtelaar G, Maione S, Di Marzo V, Calignano A, De Sarro G (2013). "Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy". Neuropharmacology. 69: 115–26. doi:10.1016/j.neuropharm.2012.11.017. PMID 23206503.

[pmid12482853-14] Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH (February 2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID 12482853.

[pmid9407140-15] Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (December 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". J. Biol. Chem. 272 (52): 33435–43. doi:10.1074/jbc.272.52.33435. PMID 9407140.

[pmid10336495-16] Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. PMID 10336495.

[pmid9626662-17] Treuter E, Albrektsen T, Johansson L, Leers J, Gustafsson JA (June 1998). "A regulatory role for RIP140 in nuclear receptor activation". Mol. Endocrinol. 12 (6): 864–81. doi:10.1210/mend.12.6.0123. PMID 9626662.

v t e PPAR modulators
PPARα	Agonists: 15-HETE 15-HpETE Aleglitazar Aluminium clofibrate Arachidonic acid Bezafibrate Clofibrate CP-775146 Daidzein DHEA (prasterone) (in rodents) Elafibranor Etomoxir Fenofibrate Genistein Gemfibrozil GW-7647 Lanifibranor Leukotriene B₄ LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoic acid Perfluorooctanoic acid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioacetic acid Troglitazone WY-14643 Antagonists: GW-6471 MK-886
PPARδ	Agonists: 15-HETE 15-HpETE Arachidonic acid Bezafibrate Daidzein Elafibranor Fonadelpar Genistein GW-0742 GW-501516 L-165,041 Lanifibranor LG-101506 Seladelpar Sodelglitazar Tetradecylthioacetic acid Antagonists: FH-535 GSK-0660 GSK-3787
PPARγ	Agonists: 5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ^12,14-prostaglandin J₂ 15-HETE 15-HpETE Aleglitazar Arachidonic acid Balaglitazone Berberine Bezafibrate Cevoglitazar Ciglitazone Daidzein Darglitazone Edaglitazone Efatutazone Englitazone Etalocib Farglitazar Genistein GW-1929 Ibuprofen Imiglitazar Indeglitazar Lanifibranor LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar (muroglitazar) nTZDpa Naveglitazar Netoglitazone Oxeglitazar Peliglitazar Pemaglitazar Perfluorononanoic acid Pioglitazone Prostaglandin J₂ Ragaglitazar Reglitazar Rivoglitazone Rosiglitazone RS5444 Saroglitazar Sipoglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone SPPARMs: BADGE EPI-001 INT-131 MK-0533 S26948 Antagonists: FH-535 GW-9662 SR-202 T-0070907 Unknown: SR-1664
Non-selective	Agonists: Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate
See also Receptor/signaling modulators Nuclear receptor modulators

リンク元	「PPAR-alpha」「ペルオキシソーム増殖剤活性化受容体α」
関連記事	「activated」「activate」「alpha」「peroxisome proliferator」「proliferator」

匿名

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案内

案内

peroxisome proliferator-activated receptor alpha