Share to: share facebook share twitter share wa share telegram print page

Plasminogen activator inhibitor-1

SERPINE1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSERPINE1, PAI, PAI-1, PAI1, PLANH1, serpin family E member 1
External IDsOMIM: 173360 MGI: 97608 HomoloGene: 68070 GeneCards: SERPINE1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001165413
NM_000602

NM_008871

RefSeq (protein)

NP_000593
NP_000593.1

NP_032897

Location (UCSC)Chr 7: 101.13 – 101.14 MbChr 5: 137.09 – 137.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor (serpin E1) is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis.[5]

PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue-type plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1).

The other PAI, plasminogen activator inhibitor-2 (PAI-2) is secreted by the placenta and only present in significant amounts during pregnancy. In addition, protease nexin acts as an inhibitor of tPA and urokinase. PAI-1, however, is the main inhibitor of the plasminogen activators.

Genetics

The PAI-1 gene is SERPINE1, located on chromosome 7 (7q21.3-q22). There is a common polymorphism known as 4G/5G in the promoter region. The 5G allele is slightly less transcriptionally active than the 4G.

Function

PAI-1's main function entails the inhibition of urokinase plasminogen activator (uPA), an enzyme responsible for the cleavage of plasminogen to form plasmin. Plasmin mediates the degradation of the extracellular matrix either by itself or in conjunction with matrix metalloproteinases. In this scenario, PAI-1 inhibits uPA via active site binding, preventing the formation of plasmin. Additional inhibition is mediated by PAI-1 binding to the uPA/uPA receptor complex, resulting in the latter's degradation.[6] Thus, PAI can be said to inhibit the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots. In addition, PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells through the basal lamina.

PAI-1 is mainly produced by the endothelium (cells lining blood vessels), but is also secreted by other tissue types, such as adipose tissue.

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Role in disease

Congenital deficiency of PAI-1 has been reported; as fibrinolysis is not suppressed adequately, it leads to a hemorrhagic diathesis (a tendency to hemorrhage).

PAI-1 is present in increased levels in various disease states (such as a number of forms of cancer), as well as in obesity and the metabolic syndrome. It has been linked to the increased occurrence of thrombosis in patients with these conditions.

PAI-1 can induce cellular senescence.[7] PAI-1 can also be a component of the senescence-associated secretory phenotype (SASP).[8]

In inflammatory conditions in which fibrin is deposited in tissues, PAI-1 appears to play a significant role in the progression to fibrosis (pathological formation of connective tissue). Presumably, lower PAI levels would lead to less suppression of fibrinolysis and conversely a more rapid degradation of the fibrin.

Angiotensin II increases the synthesis of plasminogen activator inhibitor-1, so it accelerates the development of atherosclerosis.

Pharmacology

Interactions

Plasminogen activator inhibitor-1 has been shown to interact with ORM1.[12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106366 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037411 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Vaughan DE (August 2005). "PAI-1 and atherothrombosis". Journal of Thrombosis and Haemostasis. 3 (8): 1879–1883. doi:10.1111/j.1538-7836.2005.01420.x. PMID 16102055. S2CID 6651339.
  6. ^ Carter JC, Church FC (2009). "Obesity and breast cancer: the roles of peroxisome proliferator-activated receptor-γ and plasminogen activator inhibitor-1". PPAR Research. 2009: 345320. doi:10.1155/2009/345320. PMC 2723729. PMID 19672469.
  7. ^ Zhang M, Serna-Salas S, Damba T, Borghesan M, Demaria M, Moshage H (October 2021). "Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives". Mechanisms of Ageing and Development. 199: 111572. doi:10.1016/j.mad.2021.111572. PMID 34536446. S2CID 237524296.
  8. ^ Valentijn FA, Falke LL, Nguyen TQ, Goldschmeding R (March 2018). "Cellular senescence in the aging and diseased kidney". Journal of Cell Communication and Signaling. 12 (1): 69–82. doi:10.1007/s12079-017-0434-2. PMC 5842195. PMID 29260442.
  9. ^ Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL (July 2004). "Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization". Journal of Medicinal Chemistry. 47 (14): 3491–3494. CiteSeerX 10.1.1.661.4972. doi:10.1021/jm049766q. PMID 15214776.
  10. ^ Pautus S, Alami M, Adam F, Bernadat G, Lawrence DA, De Carvalho A, et al. (November 2016). "Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1". Scientific Reports. 6: 36462. Bibcode:2016NatSR...636462P. doi:10.1038/srep36462. PMC 5120274. PMID 27876785.
  11. ^ Boe AE, Eren M, Murphy SB, Kamide CE, Ichimura A, Terry D, et al. (November 2013). "Plasminogen activator inhibitor-1 antagonist TM5441 attenuates Nω-nitro-L-arginine methyl ester-induced hypertension and vascular senescence". Circulation. 128 (21): 2318–2324. doi:10.1161/CIRCULATIONAHA.113.003192. PMC 3933362. PMID 24092817.
  12. ^ Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS (September 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". The Journal of Biological Chemistry. 276 (38): 35305–35311. doi:10.1074/jbc.M104028200. PMID 11418606.

Further reading

External links

Baca informasi lainnya:

Swedish rally driver This biography of a living person needs additional citations for verification. Please help by adding reliable sources. Contentious material about living persons that is unsourced or poorly sourced must be removed immediately from the article and its talk page, especially if potentially libelous.Find sources: Oliver Solberg – news · newspapers · books · scholar · JSTOR (January 2022) (Learn how and when to remove this template message)…

Kolkata Municipal Corporation in West Bengal, IndiaWard No. 109Kolkata Municipal CorporationInteractive Map Outlining Ward No. 109Ward No. 109Location in KolkataCoordinates: 22°28′55″N 88°24′02″E / 22.481833°N 88.400694°E / 22.481833; 88.400694Country IndiaStateWest BengalCityKolkataArea CoveredHaltu (Kalikapur), Santoshpur (Borakhola-Nandan Kanan-Purba Diganta-Survey Park), Ajoy Nagar, Hiland Park, Chak Garia, New Garia, Srinagar, Hatibari, Nayabad, Bika…

Ball used to hit pins in the sport of bowling For other uses, see Bowling ball (disambiguation). Comparative sizes of bowling balls, portrayed on boards of a bowling lane A bowling ball is a hard spherical ball used to knock down bowling pins in the sport of bowling. Balls used in ten-pin bowling and American nine-pin bowling traditionally have holes for two fingers and the thumb. Balls used in five-pin bowling, candlepin bowling, duckpin bowling, and European nine-pin bowling have no holes, and…

Irlandia UtaraJulukanGreen & White ArmyNorn IronAsosiasiAsosiasi Sepak Bola Irlandia UtaraKonfederasiUEFA (Eropa)Pelatih Ian BaracloughKaptenSteven DavisPenampilan terbanyakSteven Davis (130)Pencetak gol terbanyakDavid Healy (36)Stadion kandangWindsor ParkPeringkat FIFATerkini 75 1 (26 Oktober 2023)[1]Tertinggi27 (Agustus 2007)Terendah124 (Maret 2004)Peringkat EloTerkini 91 17 (18 Oktober 2023)[2] Warna pertama Warna kedua Pertandingan internasional pertama Irlandia Utara 0 -…

هذه المقالة يتيمة إذ تصل إليها مقالات أخرى قليلة جدًا. فضلًا، ساعد بإضافة وصلة إليها في مقالات متعلقة بها. (ديسمبر 2018) روبن وسحانداانو   معلومات شخصية الميلاد 3 أكتوبر 1980 (43 سنة)  مدريد  مواطنة إسبانيا  الحياة العملية المهنة ممثل  اللغات الإسبانية  المواقع الموق

Salidas de una simulación informática sencilla de un mundo de margaritas, en las que se aprecia la homeostasis que la biota es capaz de sostener en un cierto rango de temperatura. Mundo de margaritas (nombre original 'DaisyWorld') es una simulación publicada en 1983 que fue creada por James Lovelock y Andrew Watson para ilustrar su hipótesis Gaia. Mundo de margaritas, una simulación por ordenador o computadora, es la hipótesis de un mundo que es orbitado por un sol cuya temperatura está a…

大橋望美2009年1月的大橋望美於台北新光三越信義新天地A8館童星罗马拼音Oohashi Nozomi昵称のんちゃん(Non-chan)国籍 日本出生 (1999-05-09) 1999年5月9日(24歲)职业演員、歌手、配音員代表作品崖上的波妞活跃年代2002年-2012年经纪公司Central Group互联网电影数据库(IMDb)信息 奖项 第61回日劇學院賞助演女優賞、特別賞 日語寫法日語原文大橋 のぞみ假名おおはし のぞみ平文式…

يفتقر محتوى هذه المقالة إلى الاستشهاد بمصادر. فضلاً، ساهم في تطوير هذه المقالة من خلال إضافة مصادر موثوق بها. أي معلومات غير موثقة يمكن التشكيك بها وإزالتها. (يناير 2022) هذه المقالة يتيمة إذ تصل إليها مقالات أخرى قليلة جدًا. فضلًا، ساعد بإضافة وصلة إليها في مقالات متعلقة بها. (ي…

Haneen ZoabiLahir23 Mei 1969 (umur 54)Tempat lahirNazareth, IsraelKnesset18, 19, 20Faksi yang diwakili di Knesset2009–2015Balad2015–Joint List Haneen Zoabi, juga Hanin Zoubi (Arab: حنين زعبي, Ibrani: חנין זועבי; kelahiran 23 Mei 1969), adalah seorang Arab Palestina, dan seorang warga negara Arab di Israel, yang sekarang menjabat sebagai anggota Knesset untuk Joint List. Menjabat di Knesset sejak 2009, Zoabi adalah wanita Arab pertama yang terpilih pada parlemen …

Baden Fletcher Smyth Baden-Powell, FS, FRAS, FRMetS (* 22. Mai 1860; † 3. Oktober 1937) war ein britischer Offizier und Pionier der Militärluftfahrt und zeitweilig Präsident der Royal Aeronautical Society. Inhaltsverzeichnis 1 Familie 2 Militärische und politische Karriere 3 Weblinks 4 Einzelbelege Familie Baden Baden-Powell war der jüngste Sohn von Reverend B. Baden-Powell, der Professor für Geometrie an der Oxford University war. Sein Vater starb kurz nach seiner Geburt. Seine Mutter He…

Muni CaderCader pada tahun 1955LahirMuny Abdul Kadir(1932-02-02)2 Februari 1932Serang, Banten, Hindia BelandaMeninggal6 September 2001(2001-09-06) (umur 69)Jakarta, IndonesiaPekerjaanAktorTahun aktif1953–1955,1971–2001AnakSimon Cader Muni Cader (2 Februari 1932 – 6 September 2001)[1][2] adalah seorang aktor Indonesia. Aktor yang namanya seangkatan dengannya antara lain Doddy Sukma, Rachmat Hidayat, dan Kusno Sudjarwadi. Filmografi Film Tahun Judul Pe…

StraßenschlepperHanomag SS 100 Straßenschlepper, auch Straßenzugmaschinen oder Eilschlepper genannt, dienen dem Ziehen von Anhängern auf befestigten Wegen und Straßen. Inhaltsverzeichnis 1 Geschichte 1.1 Anfänge bis 1945 1.2 Wehrmacht 1.3 Nach 1945 2 Technik 3 Literatur 4 Einzelnachweise Geschichte Vorläufer des Straßenschleppers ist die durch eine Dampfmaschine angetriebene Lokomobile. Diese war jedoch häufig für den Betrieb auf Landstraßen zu schwer, außerdem vielfach für die zu b…

Gangkhar PuensumĐỉnh Gangkhar PuensumĐộ cao7.570 m (24.840 ft)[1]Thứ 40Phần lồi2.995 m (9.826 ft)[1]Thứ 92Danh sáchDanh sách điểm caoUltraVị tríGangkhar PuensumVị trí Gangkhar Puensum ở BhutanVị tríBiên giới Bhutan–TQDãy núiHimalayaTọa độ28°02′54″B 90°27′15″Đ / 28,04833°B 90,45417°Đ / 28.04833; 90.45417[1]Leo núiChinh phục lần đầuChưa có Gangkhar Puensum (tiếng …

Fleur des champs (1845) Louis Janmot Wikimedia Commons has media related to Lyon School. The Lyon School (French: École de Lyon) is a term for a group of French artists which gathered around Paul Chenavard. It was founded by Pierre Revoil, one of the representatives of the Troubadour style. It included Victor Orsel, Louis Janmot and Hippolyte Flandrin, and was nicknamed the prison of painting by Charles Baudelaire. It was principally inspired by philosophical-moral and religious themes, and as …

Пасхальные марши мира в Германии — ежегодно проводимые в Пасху в городах Германии мирные акции, целью которых является выражение протеста против войн и применения оружия. Пасхальные марши проводятся в Германии с начала 1960-х годов по инициативе известного в стране стор…

Indian mixed martial arts promoter See also: Super Boxing League Super Fight LeagueTypePrivateIndustryMixed martial arts promotionFounded2012; 11 years ago (2012)FounderSanjay DuttRaj KundraDefunct2018HeadquartersIndiaOwnerBill DosanjhAmir Khan[1]WebsiteOfficial website Super Fight League was a mixed martial arts promotion, based in India. The organisation was formed in 2012 by actor Sanjay Dutt and British-Indian businessman Raj Kundra,[2] and is currently co-o…

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Zorro novel – news · newspapers · books · scholar · JSTOR (April 2016) (Learn how and when to remove this template message) Zorro First edition coverAuthorIsabel AllendeOriginal titleEl Zorro: Comienza la leyendaTranslatorMargaret Sayers PedenCountryChil…

Dieser Artikel oder nachfolgende Abschnitt ist nicht hinreichend mit Belegen (beispielsweise Einzelnachweisen) ausgestattet. Angaben ohne ausreichenden Beleg könnten demnächst entfernt werden. Bitte hilf Wikipedia, indem du die Angaben recherchierst und gute Belege einfügst. Mustafa Akıncı 2015 Mustafa Akıncı im Gespräch mit US-Außenminister John Kerry Mustafa Akıncı (* 28. Dezember 1947 in Limassol) ist ein türkisch-zyprischer Politiker. Er war vom 30. April 2015 bis 23. Oktober 202…

Enlightening the World Студийный альбом Undercode Дата выпуска 19 сентября 2002 года Дата записи апрель — октябрь 2001 Место записи Студия Monitor Audio, (Загреб, Хорватия) Жанр Хеви-метал Продюсеры Davor Keranovic Ivan Speljak - Jitz Страна  Хорватия Лейбл Metal Warriors Хронология Undercode Enlightening the World(2002) Post-Apocalyptic(2015)…

Extended-range classical guitar 11-string alto guitar Head of 11-string alto guitar The eleven-string alto guitar (also known as altgitarr, archguitar, or Bolin guitar) is an extended-range classical guitar developed by Swedish luthier Georg Bolin in the 1960s. Original Bolin instruments are now rare and valuable.[1] The Bolin alto guitar most often has eleven strings, but Bolin also made a thirteen-string version. The 11-string alto guitar is a multi-string classical guitar, which gener…

Rail station in Latvia Riga Central StationRīgas Centrālā stacijaGeneral informationOther namesRīgas Pasažieru stacijaLocationStacijas laukums 2Centra rajonsRīga LV-1050LatviaOwned byLatvian RailwaysLine(s)Riga–TukumsRiga–JelgavaRiga–DaugavpilsRiga–LugažiRiga–SkultePlatforms5Tracks12Connectionsbus, trolleybusHistoryOpened1861LocationRiga Central StationLocation within Latvia Riga Central Station (Latvian: Rīgas Centrālā stacijа) is the main railway station in Riga, Latvia. I…

Queen Street, one of the major roads in Brisbane, after the 1893 floods. Residents are seen rowing boats to move about due to the flooding. South Brisbane during the 1893 flood. Map from the Irrigation and Water Supply Commission. Albert Bridge The 1893 Brisbane flood, occasionally referred to as the Great Flood of 1893 or the Black February flood, occurred in 1893 in Brisbane, Queensland, Australia. The Brisbane River burst its banks on three occasions in February 1893. It was the occurrence of…

Voce principale: Copa México. Indice 1 Albo d'oro 1.1 Copa Tower (1907 - 1921) 1.2 Copa Eliminatoria (1921 - 1926) 1.3 Copa México (1932 - oggi) 1.3.1 Periodo amatoriale (1932 - 1943) 1.3.2 Periodo professionistico (1943 - oggi) 2 Note Albo d'oro Elenco dei vincitori delle edizioni della Copa México disputate dal 1907 a oggi. Copa Tower (1907 - 1921) Anno Vincitore Sfidante Punteggio 1907-1908  Pachuca  Reforma 4-0 1908-1909  Reforma  México FC 3-2 1909-1910  Reforma…

Jonathan Krisel, Fred Armisen, Carrie Brownstein en Lorne Michaels bij de Peabody Awards 2012 Portlandia is een Amerikaanse sketch comedy uit 2011. De serie werd opgenomen in Portland, Oregon en de titel verwijst naar de gelijknamige sculptuur boven de ingang van het Portland Building. De satirische sketch wordt gemaakt door Fred Armisen, Carrie Brownstein en Jonathan Krisel. De eerste twee nemen de meeste rollen op zich. Verschillende bekende acteurs en musici hebben een kleine (meestal eenmali…

Fugees Datos generalesOrigen West Orange, Nueva Jersey,  Estados UnidosInformación artísticaGénero(s) Rap, Reggae, Rhythm and blues, SoulPeríodo de actividad 1989 - 1997 2004 - 2007Discográfica(s) Columbia RecordsWebSitio web Sitio web oficialMiembros Wyclef Jean Lauryn Hill Pras [editar datos en Wikidata] Fugees fue un grupo estadounidense de rap y rhythm and blues formado en West Orange, Nueva Jersey, en 1989.[1]​ Su repertorio incluye sobre todo hip hop, co…

日本の政治家川崎 二郎かわさき じろう 2019年 中勢バイパス開通式にて生年月日 (1947-11-15) 1947年11月15日(76歳)出生地 日本 三重県伊賀市[1]出身校 慶應義塾大学商学部[1]前職 松下電器産業(現:パナソニック)社員[1]所属政党 自由民主党(谷垣派→古賀派→谷垣G)称号 商学士旭日大綬章子女 長男・川崎秀人(衆議院議員)親族 祖父・川崎克(元衆議院…

12世紀に作られた聖母マリアの墓の正面 平面図と垂直断面図 岩を削り作られた聖母マリアの墓、墓の玄関、イコンに覆われた前面(地下聖堂の東部後陣) 聖母マリアの遺体の上にある石のベンチは展示されており、現在はガラス越しに見ることが可能。 地図 聖母マリア墳墓教会(せいぼマリアふんぼきょうかい)、別名聖母マリアの墓はエルサレムのオリーブ山の麓の…

Questa voce sull'argomento calciatori tedeschi è solo un abbozzo. Contribuisci a migliorarla secondo le convenzioni di Wikipedia. Segui i suggerimenti del progetto di riferimento. Markus Oberleitner Nazionalità  Germania Altezza 178 cm Calcio Ruolo Centrocampista Termine carriera 2003 Carriera Squadre di club1 1994-1996 Unterhaching58 (18)1996-1997 Bayern Monaco0 (0)1997→  Fortuna Düsseldorf13 (0)1997-2001 Unterhaching111 (11)2001 Greuther Fürth2 (0)2001-…

Voce principale: Roma Calcio Femminile. A.C.F. Roma ItalparatiStagione 1977Sport calcio Squadra Roma Italparati Allenatore Presidente Italia Farina Serie A10º posto. Coppa Italia???. 1976 1978 Si invita a seguire il modello di voce Questa voce raccoglie le informazioni riguardanti la Associazione Calcio Femminile Roma Italparati nelle competizioni ufficiali della stagione 1977. Indice 1 La stagione 2 Rosa 3 Note 4 Bibliografia La stagione Questa sezione sull'argomento stagioni delle s…

Species of rodent Island mouse Conservation status Least Concern (IUCN 3.1)[1] Scientific classification Domain: Eukaryota Kingdom: Animalia Phylum: Chordata Class: Mammalia Order: Rodentia Family: Nesomyidae Genus: Nesomys Species: N. rufus Binomial name Nesomys rufusPeters, 1870 Island mouse range The island mouse[1] or eastern red forest rat[1] (Nesomys rufus) is a species of rodent in the family Nesomyidae.[2] It is endemic to Madagascar. References …

Kembali kehalaman sebelumnya