ペルオキシソーム増殖剤活性化受容体β、PPARβ、PPAR-β

関: peroxisome proliferator-activated receptor beta

WordNet

to remain unmolested, undisturbed, or uninterrupted -- used only in infinitive form; "let her be"
work in a specific place, with a specific subject, or in a specific function; "He is a herpetologist"; "She is our resident philosopher" (同)follow
have life, be alive; "Our great leader is no more"; "My grandfather lived until the end of war" (同)live
be identical to; be someone or something; "The president of the company is John Smith"; "This is my house"
happen, occur, take place; "I lost my wallet; this was during the visit to my parents house"; "There were two hundred people at his funeral"; "There was a lot of noise in the kitchen"
have the quality of being; (copula, used with an adjective or a predicate noun); "John is rich"; "This is not a good answer"
occupy a certain position or area; be somewhere; "Where is my umbrella?" "The toolshed is in the back"; "What is behind this behavior?"
spend or use time; "I may be an hour"
stake on the outcome of an issue; "I bet $100 on that new horse"; "She played all her money on the dark horse" (同)wager, play
the act of gambling; "he did it on a bet" (同)wager
maintain with or as if with a bet; "I bet she will be there!" (同)wager
second in order of importance; "the candidate, considered a beta male, was perceived to be unable to lead his party to victory"
the 2nd letter of the Greek alphabet
preliminary or testing stage of a software or hardware product; "a beta version"; "beta software"

PrepTutorEJDIC

《連結語として補語を伴なって…『である』,…だ,…です / 《位置・場所を表す語句を伴って》(…に)『ある』,いる(occupy a place or situation) / 〈物事が〉『存在する』,ある(exist);〈生物が〉生存する,生きている(live) / 行われる,起こる,発生する(take place, occur) / 存続する,そのままでいる(remain as before) / 《『be to』 do》 / …する予定である,…することになっている / …すべきだ / 《受動態の不定詞を伴って》…できる / 《命令》…するのだ / 《条件節に》…する意図がある / 《『if…were to』 do》…するとしたなら / 《『be』 do『ing』》《進行形》 / 《進行中の動作》…している,しつつある / 《近い未来》…しようとしている,するつもり / 《動作の反復》(いつも)…している / 《『be』+『他動詞の過去分詞』》《受動態》…される,されている / 《『be』+『自動詞の過去分詞』》《完了形》…した[状態にある]
『かけ』・(…との)かけ《+『with』+『名』》 / かけた物(金) / かけの対象 / 〈金・物〉'を'『かける』 / (かけ事・ゲームなどで)〈人〉‘と'『かけをする』《+『名』〈人〉+『on』+『名』》 / (…に)『かける』《+『on』(『against』)+『名』(one's do『ing』)》
ベータ(ギリシア語アルファベットの第2文字;B,β;英語のB,b に遭当)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/31 10:44:49」(JST)

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[Wiki en表示]

Peroxisome proliferator-activated receptor beta or delta (PPAR-β or PPAR-δ), also known as NR1C2 (nuclear receptor subfamily 1, group C, member 2) is a nuclear receptor that in humans is encoded by the PPARD gene.^[1]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in Xenopus in 1993.^[2]

Function[edit]

PPARδ is a nuclear hormone receptor that governs a variety of biological processes and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer.^[3]^[4]

PPARδ may function as an integrator of transcription repression and nuclear receptor signaling. It activates transcription of a variety of target genes by binding to specific DNA elements. Well described target genes of PPARδ include PDK4, ANGPTL4, PLIN2, and CD36. The expression of this gene is found to be elevated in colorectal cancer cells.^[5] The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein involved in the APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, epidermal cell proliferation, and glucose^[6] and lipid metabolism.^[7]

This protein has been shown to be involved in differentiation, lipid accumulation,^[8] directional sensing, polarization, and migration in keratinocytes.^[9]

Role in cancer[edit]

Studies into the role of PPAR-δ in cancer have produced contradictory results and there is no scientific consensus on whether it promotes or prevents cancer formation.^[10]^[11]

Clinical significance[edit]

In one study, polymorphisms of PPARD were found to be associated with bipolar disorder.^[12]

Pharmacology[edit]

Several high affinity ligands for PPAR-δ/β have been developed, including GW 501516 and GW0742, which play an important role in research. In one study utilizing such a ligand, it has been shown that agonism of PPAR-δ changes the body's fuel preference from glucose to lipids.^[13]

Tissue distribution[edit]

PPAR-δ/β is highly expressed in many tissues, including colon, small intestine, liver and keratinocytes, as well as in heart, spleen, skeletal muscle, lung, brain and thymus.^[14]

Knockout studies[edit]

Knockout mice lacking the ligand binding domain of PPAR-δ/β are viable. However these mice are smaller than the wild type both neo and postnatally. In addition, fat stores in the gonads of the mutants are smaller. The mutants also display increased epidermal hyperplasia upon induction with TPA.^[15]

Ligands[edit]

PPARδ is activated in the cell by various fatty acids and fatty acid derivatives. Several synthetic ligands have been identified that selectively bind PPARδ.

Agonists[edit]

GW-501,516
GW0742^[16]

Interactions[edit]

Peroxisome proliferator-activated receptor delta has been shown to interact with HDAC3^[17]^[18] and NCOR2.^[18]

References[edit]

^ Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA (1992). "Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids". Mol. Endocrinol. 6 (10): 1634–41. doi:10.1210/me.6.10.1634. PMID 1333051.
^ Krey G, Keller H, Mahfoudi A, Medin J, Ozato K, Dreyer C, Wahli W (1993). "Xenopus peroxisome proliferator activated receptors: genomic organization, response element recognition, heterodimer formation with retinoid X receptor and activation by fatty acids". J Steroid Biochem Mol Biol. 47 (1–6): 65–73. doi:10.1016/0960-0760(93)90058-5. PMID 8274443.
^ Berger J, Moller DE (2002). "The mechanisms of action of PPARs". Annu. Rev. Med. 53: 409–35. doi:10.1146/annurev.med.53.082901.104018. PMID 11818483.
^ Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W (2006). "From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions". Prog. Lipid Res. 45 (2): 120–59. doi:10.1016/j.plipres.2005.12.002. PMID 16476485.
^ Takayama O, Yamamoto H, Damdinsuren B, Sugita Y, Ngan CY, Xu X, Tsujino T, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M (2006). "Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology". Br. J. Cancer 95 (7): 889–95. doi:10.1038/sj.bjc.6603343. PMC 2360534. PMID 16969348.
^ Lee CH, Olson P, Hevener A, Mehl I, Chong LW, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, Evans RM (2006). "PPARδ regulates glucose metabolism and insulin sensitivity". Proc. Natl. Acad. Sci. U.S.A. 103 (9): 3444–9. doi:10.1073/pnas.0511253103. PMC 1413918. PMID 16492734.
^ "Entrez Gene: PPARD peroxisome proliferator-activated receptor delta".
^ Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S, Lau P, Fowler AJ, Chuang G, Moser AH, Brown BE, Mao-Qiang M, Uchida Y, Schoonjans K, Auwerx J, Chambon P, Willson TM, Elias PM, Feingold KR (April 2004). "Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes". J. Invest. Dermatol. 122 (4): 971–83. doi:10.1111/j.0022-202X.2004.22412.x. PMID 15102088.
^ Tan NS, Icre G, Montagner A, Bordier-ten-Heggeler B, Wahli W, Michalik L (October 2007). "The Nuclear Hormone Receptor Peroxisome Proliferator-Activated Receptor β/δ Potentiates Cell Chemotactism, Polarization, and Migration". Mol. Cell. Biol. 27 (20): 7161–75. doi:10.1128/MCB.00436-07. PMC 2168901. PMID 17682064.
^ Tachibana K, Yamasaki D, Ishimoto K, Doi T (2008). "The Role of PPARs in Cancer". PPAR Res 2008: 102737. doi:10.1155/2008/102737. PMC 2435221. PMID 18584037.
^ Peters JM, Shah YM, Gonzalez FJ (March 2012). "The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention". Nat. Rev. Cancer 12 (3): 181–95. doi:10.1038/nrc3214. PMC 3322353. PMID 22318237.
^ Zandi PP, Belmonte PL, Willour VL, Goes FS, Badner JA, Simpson SG, Gershon ES, McMahon FJ, DePaulo JR Jr, Potash JB; Bipolar Disorder Phenome Group; National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium (July 2008). "Association Study of Wnt Signaling Pathway Genes in Bipolar Disorder". Arch. Gen. Psychiatry 65 (7): 785–93. doi:10.1001/archpsyc.65.7.785. PMC 3170992. PMID 18606951.
^ Brunmair B, Staniek K, Dörig J, Szöcs Z, Stadlbauer K, Marian V, Gras F, Anderwald C, Nohl H, Waldhäusl W, Fürnsinn C (November 2006). "Activation of PPAR-δ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids". Diabetologia 49 (11): 2713–22. doi:10.1007/s00125-006-0357-6. PMID 16960684.
^ Girroir EE, Hollingshead HE, He P, Zhu B, Perdew GH, Peters JM (July 2008). "Quantitative expression patterns of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) protein in mice". Biochem. Biophys. Res. Commun. 371 (3): 456–61. doi:10.1016/j.bbrc.2008.04.086. PMC 2586836. PMID 18442472.
^ Peters JM, Lee SS, Li W, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD, Gonzalez FJ. (1993). "Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome Proliferator-Activated Receptor β(δ)". Mol Cell Biol. 20 (14): 5119–28. doi:10.1128/MCB.20.14.5119-5128.2000. PMC 85961. PMID 10866668.
^ van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F (March 2005). "Reduced cholesterol absorption upon PPAR-δ activation coincides with decreased intestinal expression of NPC1L1". J. Lipid Res. 46 (3): 526–34. doi:10.1194/jlr.M400400-JLR200. PMID 15604518.
^ Franco PJ, Li G, Wei LN (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Mol. Cell. Endocrinol. 206 (1–2): 1–12. doi:10.1016/S0303-7207(03)00254-5. PMID 12943985.
^ ^a ^b Shi Y, Hon M, Evans RM (March 2002). "The peroxisome proliferator-activated receptor δ, an integrator of transcriptional repression and nuclear receptor signaling". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2613–8. doi:10.1073/pnas.052707099. PMC 122396. PMID 11867749.

External links[edit]

PPAR delta 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.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 糖尿病の治療におけるチアゾリジン thiazolidinediones in the treatment of diabetes mellitus
2. 大腸癌の分子遺伝学 molecular genetics of colorectal cancer
3. 虚血後（虚血性）の急性尿細管壊死の発症および病因 pathogenesis and etiology of postischemic ischemic acute tubular necrosis
4. 2型糖尿病の病因 pathogenesis of type 2 diabetes mellitus
5. 糖尿病性腎症の治療 treatment of diabetic nephropathy

English Journal

The effects of kefir, koumiss, yogurt and commercial probiotic formulations on PPARα and PPAR-β/δ expressions in mouse kidney.

Sari E1, Bakir B, Aydin B, Sozmen M.Author information 1Department of Histology-Embryology, Faculty of Veterinary Medicine, University of Kafkas , 36040 Kars.AbstractAbstract Commercial probiotic capsules that contain probiotic bacteria, kefir, koumiss and yogurt contain beneficial microorganisms that affect cholesterol levels and immune response, and are used for treatment of some diseases. We investigated using immunohistochemistry the effects of kefir, koumiss, yogurt and a commercial probiotic formulation on the expression levels of peroxisome proliferator-activated receptor-α (PPARα) and peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ), which are members of the nuclear steroid hormone receptor superfamily in mouse kidney. Mice were assigned to five groups: group 1, commercial probiotic capsules; group 2, kefir; group 3, koumiss; group 4, yogurt; group 5, control. After oral administration for 15 days, body weights were recorded and kidney tissue samples were obtained. Hematoxylin & eosin staining and the streptavidin-biotin peroxidase complex (ABC) method were applied to tissue sections to examine histology and to determine the localization of PPARα and PPAR-β/δ in the kidneys. We found that the weights of the mice in the kefir, koumiss, yogurt and commercial probiotic capsules groups were increased compared to controls. No differences in kidney histology were observed in any of the experimental groups. Kefir, koumiss, yogurt and the commercial probiotic preparation increased PPARα and PPAR-β/δ expressions.
Biotechnic & histochemistry : official publication of the Biological Stain Commission.Biotech Histochem.2014 May;89(4):287-95. doi: 10.3109/10520295.2013.844274. Epub 2013 Nov 10.
Abstract Commercial probiotic capsules that contain probiotic bacteria, kefir, koumiss and yogurt contain beneficial microorganisms that affect cholesterol levels and immune response, and are used for treatment of some diseases. We investigated using immunohistochemistry the effects of kefir, koumis
PMID 24205877

Identification of suitable reference genes for quantitative RT-PCR during 3T3-L1 adipocyte differentiation.

Zhang J1, Tang H1, Zhang Y1, Deng R1, Shao L2, Liu Y1, Li F1, Wang X1, Zhou L1.Author information 1Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.2Department of Geratology, East Hospital, Shanghai Tongji University, Shanghai 200120, P.R. China.AbstractQuantitative reverse transcription PCR (qRT-PCR) is becoming increasingly important in the effort to gain insight into the molecular mechanisms underlying adipogenesis. However, the expression proﬁle of a target gene may be misinterpreted due to the unstable expression of the reference genes under different experimental conditions. Therefore, in this study, we investigated the expression stability of 10 commonly used reference genes during 3T3-L1 adipocyte differentiation. The mRNA expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and transferrin receptor (TFRC) significantly increased during the course of 3T3-L1 adipocyte differentiation, which was decreased by berberine, an inhibitor of adipogenesis. Three popular algorithms, GeNorm, NormFinder and BestKeeper, identified 18 ribosomal RNA and hydroxymethylbilane synthase (HMBS) as the most stable reference genes, while GAPDH and TFRC were the least stable ones. Peptidylprolyl isomerase A [PIPA (cyclophilin A)], ribosomal protein, large, P0 (36-B4), beta-2-microglobulin (B2M), α1-tubulin, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and β-actin showed relatively stable expression levels. The choice of reference genes with various expression stabilities exerted a profound influence on the expression profiles of 2 target genes, peroxisome proliferator-activated receptor (PPAR)γ2 and C/EBPα. In addition, western blot analysis revealed that the increased protein expression of GAPDH was markedly inhibited by berberine during adipocyte differentiation. This study highlights the importance of selecting suitable reference genes for qRT-PCR studies of gene expression during the process of adipogenesis.
International journal of molecular medicine.Int J Mol Med.2014 May;33(5):1209-18. doi: 10.3892/ijmm.2014.1695. Epub 2014 Mar 11.
Quantitative reverse transcription PCR (qRT-PCR) is becoming increasingly important in the effort to gain insight into the molecular mechanisms underlying adipogenesis. However, the expression proﬁle of a target gene may be misinterpreted due to the unstable expression of the reference genes under
PMID 24626784

Metalloproteinase dependent reduction of cell surface cluster determinants upon the induction of apoptosis.

Magro A1, Magro A1, Shrestha S2, Brundage K3, Rankin G4.Author information 1Department of Biology, Fairmont State University, Fairmont, WV, USA.2Department of Statistics, West Virginia University, Morgantown, WV, USA.3Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, USA.4Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.AbstractLN18 glioblastoma cells were used as a model to examine changes in surface cluster determinants (CDs) as the cells undergo apoptosis. LN18 cells proceeding through apoptosis manifested a decrease in cell adhesion molecules, growth factor receptors and other surface proteins. Apoptosis was induced by MK886, a known FLAP and PPAR-α inhibitor, or staurosporine, a known inhibitor of protein kinases including protein kinase C (PKC). The detection and decrease of surface CDs were observed by flow cytometry using CD-specific primary antibodies followed by secondary antibodies conjugated to phycoerythrin. It was determined that there was an apoptotic induced decrease of α and β integrin determinants and the growth factor receptors EGFR and IGF1R. The MHC-1 cell surface marker HLA-ABC was also reduced in the apoptotic cells. The level of EGFR, IGF1R and detected α and β integrin determinants dropped dramatically. The degradation takes place in mid to late apoptosis. It was determined by real-time RT-PCR that the decrease in integrins, EGFR, IGF1R and MHC-1 determinants were not due to a reduction in transcription. Inhibitors of metallo-proteinases blocked the apoptotic decrease in cell surface determinants indicating that metalloproteinases mediated the reduction in these CDs in a manner that can reduce growth and survival signals while stimulating the NK surveillance system. Overall, the data indicate that the final stages of the pharmacological induction of apoptosis, while proceeding to a full commitment to non-necrotic cell death, involves the degradation of integrin, insulin and epidermal growth factor receptors caused by a programmed dysregulation of the cell's metalloproteinases.
International journal of oncology.Int J Oncol.2014 May;44(5):1539-50. doi: 10.3892/ijo.2014.2344. Epub 2014 Mar 13.
LN18 glioblastoma cells were used as a model to examine changes in surface cluster determinants (CDs) as the cells undergo apoptosis. LN18 cells proceeding through apoptosis manifested a decrease in cell adhesion molecules, growth factor receptors and other surface proteins. Apoptosis was induced by
PMID 24626736

Japanese Journal

PPAR.BETA./.DELTA. regulates the human SIRT1 gene transcription via Sp1

Okazaki Mizuho,Iwasaki Yasumasa,Nishiyama Mitsuru,Taguchi Takafumi,Tsugita Makoto,Nakayama Shuichi,Kambayashi Machiko,Hashimoto Kozo,Terada Yoshio
Endocrine Journal 57(5), 403-413, 2010
… PPARα and PPARγ1 without/with their specific ligands did not have significant effect as well. … In contrast, expression of PPARβ/δ (PPARδ markedly increased the 5' -promoter activity of SIRT1 gene, which was further amplified by the addition of GW501516, a selective PPARδ agonist. …
NAID 130004443623

PPAR-beta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway

VARNAT F
Gastroenterology 131, 538-553, 2006
NAID 30023001769

Related Pictures

★リンクテーブル★

リンク元	「PPARβ」「PPAR-β」「ペルオキシソーム増殖剤活性化受容体β」「peroxisome proliferator-activated receptor beta」
関連記事	「PPAR」「PP」「PPA」「beta」「be」

「PPARβ」

Peroxisome proliferator-activated receptor delta
	; PDB rendering based on 1gwx.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1GWX, 1Y0S, 2AWH, 2B50, 2BAW, 2ENV, 2GWX, 2J14, 2Q5G, 2XYJ, 2XYW, 2XYX, 2ZNP, 2ZNQ, 3D5F, 3DY6, 3ET2, 3GWX, 3GZ9, 3OZ0, 3PEQ, 3SP9, 3TKM
Identifiers
Symbols	PPARD; FAAR; NR1C2; NUC1; NUCI; NUCII; PPARB
External IDs	OMIM: 600409 MGI: 101884 HomoloGene: 4544 IUPHAR: NR1C2 ChEMBL: 3979 GeneCards: PPARD Gene
Gene Ontology
Molecular function	• DNA binding; • sequence-specific DNA binding transcription factor activity; • steroid hormone receptor activity; • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; • fatty acid binding; • drug binding; • zinc ion binding; • lipid binding; • sequence-specific DNA binding; • linoleic acid binding;
Cellular component	• nucleus; • nucleoplasm;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • glucose metabolic process; • generation of precursor metabolites and energy; • regulation of transcription from RNA polymerase II promoter; • transcription initiation from RNA polymerase II promoter; • lipid metabolic process; • fatty acid beta-oxidation; • apoptotic process; • embryo implantation; • cholesterol metabolic process; • cell proliferation; • positive regulation of cell proliferation; • axon ensheathment; • fatty acid catabolic process; • gene expression; • positive regulation of phosphatidylinositol 3-kinase cascade; • glucose transport; • fatty acid transport; • cell differentiation; • intracellular receptor signaling pathway; • cell-substrate adhesion; • wound healing; • anagen; • keratinocyte proliferation; • positive regulation of fat cell differentiation; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • decidualization; • negative regulation of epithelial cell proliferation; • keratinocyte migration; • adipose tissue development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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