プラスミノーゲン活性化因子インヒビター1、プラスミノーゲンアクチベーターインヒビター1

関: PAI-1

WordNet

limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
limit the range or extent of; "Contact between the young was inhibited by strict social customs"
a substance that retards or stops an activity
(biology) any agency bringing about activation; a molecule that increases the activity of an enzyme or a protein that increases the production of a gene product in DNA transcription
an inactive form of plasmin that occurs in plasma and is converted to plasmin by organic solvents

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〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
抑制する人(物) / 化学反応抑制剤

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/04 03:04:05」(JST)

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[Wiki en表示]

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene.

PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue 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[edit]

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[edit]

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

PAI-1 inhibits the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots.

PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells across the basal lamina.

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

Role in disease[edit]

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.

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

Pharmacology[edit]

Tiplaxtinin (PAI-039) is a small molecule inhibitor that is being studied for use in the attenuation of remodeling of blood vessels, a result of arterial hypertension and activation of the renin-angiotensin system.^[1]

Interactions[edit]

Plasminogen activator inhibitor-1 has been shown to interact with ORM1.^[2]

References[edit]

^ Elokdah H, Abou-Gharbia M, Hennan JK, et al. (July 2004). "Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization". J. Med. Chem. 47 (14): 3491–4. doi:10.1021/jm049766q. PMID 15214776.
^ Boncela, J; Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski C S (Sep. 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". J. Biol. Chem. (United States) 276 (38): 35305–11. doi:10.1074/jbc.M104028200. ISSN 0021-9258. PMID 11418606.

External links[edit]

The MEROPS online database for peptidases and their inhibitors: I04.020
Plasminogen Activator Inhibitor 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 血栓溶解異常による血栓性および出血性疾患 thrombotic and hemorrhagic disorders due to abnormal fibrinolysis
2. 線溶マーカーおよび心血管リスク fibrinolytic markers and cardiovascular risk
3. 止血の概要 overview of hemostasis
4. 下肢末梢動脈疾患の症状を治療するための試験的治療 investigational therapies for treating symptoms of lower extremity peripheral artery disease
5. 血管内皮機能および血栓溶解療法の基本的メカニズム vascular endothelial function and fundamental mechanisms of fibrinolysis thrombolysis

English Journal

Heparanase procoagulant activity, factor Xa, and plasminogen activator inhibitor 1 are increased in shift work female nurses.

Nadir Y1, Saharov G, Hoffman R, Keren-Politansky A, Tzoran I, Brenner B, Shochat T.
Annals of hematology.Ann Hematol.2015 Jul;94(7):1213-9. doi: 10.1007/s00277-015-2345-8. Epub 2015 Mar 7.
Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underling mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation syst
PMID 25743687

Evaluation of Lp-PLA2 mass, vitronectin and PAI-1 activity levels in patients with preeclampsia.

Balcı Ekmekçi Ö1, Ekmekçi H, Güngör Z, Tüten A, Toprak MS, Korkmaz M, Öncül M, Çalışkan O, Kucur M, Donma O, Madazlı R, Sönmez H.
Archives of gynecology and obstetrics.Arch Gynecol Obstet.2015 Jul;292(1):53-8. doi: 10.1007/s00404-014-3601-1. Epub 2014 Dec 20.
PURPOSE: The aim of the current study is to determine, correlate and compare the plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), vitronectin (Vn), Plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (t-PA) levels in early-onset preeclampsia, late-onset preec
PMID 25527349

Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis.

Burns TA1, Watts MR1, Weber PS2, McCutcheon LJ3, Geor RJ2, Belknap JK1.
Equine veterinary journal.Equine Vet J.2015 Jul;47(4):489-93. doi: 10.1111/evj.12314. Epub 2014 Sep 10.
REASONS FOR PERFORMING STUDY: Acute, massive enteral carbohydrate overload is associated with laminar inflammation in equids; it is unclear if the same is true for a more prolonged period of moderate dietary carbohydrate intake.OBJECTIVES: To characterise laminar inflammation in ponies exposed to a
PMID 24963607

Japanese Journal

フィトケミカルの保健機能についての検討

高橋君子,飯塚美伸,石橋克之 [他],宍戸昌一郎,谷口亜希子,眞鍋久
鎌倉女子大学紀要 (22), 1-11, 2015-03-31
肥満解消に植物性化学物質 (フィトケミカル) が有効であることが示唆されている。そこでマウス脂肪細胞へソバ含有のルチンを作用させ、悪玉アディポサイトカインである PAI-1 産生を測定した。ルチン添加で濃度依存的に PAI-1 mRNA 発現量の増加が認められたが、分泌量およびその活性の減少には有意差を認めなかった。一方ルチンによる脂肪分解酵素発現は、用量依存的に増加した。この結果は …
NAID 110009893263

加齢と血栓傾向

山本晃士
日本血栓止血学会誌 26(3), 265-271, 2015
NAID 130005078051

Effects of Body Mass Index on the Lipid Profile and Biomarkers of Inflammation and a Fibrinolytic and Prothrombotic State

Orenes-Piñero Esteban,Pineda Javier,Roldán Vanessa,Hernández-Romero Diana,Marco Pascual,Tello-Montoliu Antonio,Sogorb Francisco,Valdés Mariano,Lip Gregory Y.H.,Marín Francisco
Journal of Atherosclerosis and Thrombosis 22(6), 610-617, 2015
… also measured the serum/plasma lipid, fibrinogen, D-dimer, von Willebrand factor, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) and high-sensitivity C-reactive protein (CRP-hs) levels in samples of peripheral blood.Results: The subjects with premature ischaemic heart disease and hypertension had higher BMI values (p＜0.01), and the subjects with an increased weight showed an unadjusted detrimental …
NAID 130005078029

「PAI-1」

Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
	; PAI-1 in complex with the SMB domain of Vitronectin PDB 1OC0
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1A7C, 1B3K, 1C5G, 1DB2, 1DVM, 1DVN, 1LJ5, 1OC0, 3CVM, 3EOX, 3PB1, 3Q02, 3Q03, 3R4L, 3UT3, 4AQH, 9PAI
Identifiers
Symbols	SERPINE1; PAI; PAI-1; PAI1; PLANH1
External IDs	OMIM: 173360 MGI: 97608 HomoloGene: 68070 ChEMBL: 3475 GeneCards: SERPINE1 Gene
Gene Ontology
Molecular function	• protease binding; • serine-type endopeptidase inhibitor activity; • receptor binding; • protein binding;
Cellular component	• extracellular region; • extracellular space; • plasma membrane; • extracellular matrix; • platelet alpha granule lumen;
Biological process	• chronological cell aging; • angiogenesis; • platelet degranulation; • transcription, DNA-dependent; • transcription initiation from RNA polymerase II promoter; • transforming growth factor beta receptor signaling pathway; • blood coagulation; • gene expression; • regulation of receptor activity; • negative regulation of plasminogen activation; • negative regulation of endopeptidase activity; • negative regulation of smooth muscle cell migration; • platelet activation; • positive regulation of blood coagulation; • negative regulation of blood coagulation; • negative regulation of cell migration; • positive regulation of interleukin-8 production; • negative regulation of cell adhesion mediated by integrin; • positive regulation of leukotriene production involved in inflammatory response; • regulation of cell proliferation; • fibrinolysis; • negative regulation of apoptotic process; • positive regulation of angiogenesis; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of receptor-mediated endocytosis; • positive regulation of inflammatory response; • defense response to Gram-negative bacterium; • negative regulation of fibrinolysis; • negative regulation of vascular wound healing; • negative regulation of wound healing; • cellular response to chemical stimulus; • cellular response to lipopolysaccharide; • positive regulation of monocyte chemotaxis; • negative regulation of smooth muscle cell-matrix adhesion;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: plasminogen activator inhibitor 1
関: プラスミノゲンアクティベーター・インヒビター1, プラスミノゲン活性化因子インヒビター1、プラスミノーゲン活性化因子阻害物質1

酸性組織：血管壁、肝臓、脂肪細胞

PAI-1はPAと急速に結合し複合体を形成してPAを阻止する。
血中濃度が高値

血栓の溶解が阻害　→　血栓による多臓器不全
播種性血管内凝固、敗血症、全身性炎症反応症候群　→　PAI-1高値

血管内皮細胞障害　→　PAI-1放出

「プラスミノーゲンアクチベーターインヒビター1」

　　[★]

英: plasminogen activator inhibitor 1, PAI-1
同: プラスミノーゲン活性化因子インヒビター1、プラスミノゲン活性化因子阻害因子1
関: プラスミノーゲンアクチベーターインヒビター

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プラスミノゲンアクチベーターインヒビター1 : 約 7,730 件
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「plasminogen activator inhibitor 1 deficiency」

　　[★] プラスミノゲンアクチベーターインヒビター1欠乏症

「plasminogen activator inhibitor-1」

　　[★] プラスミノゲンアクチベータインヒビター-1

「inhibit」

　　[★]

v.

抑制する、阻害する、阻止する

関: abrogate、block、depress、depression、deter、inhibition、interdict、prevent、prevention、repress、repression、restrain、restraint、suppress、suppression

「inhibitor」

　　[★]

n.

阻害剤、阻害薬、抑制薬、抑制剤、(内在性物質について)インヒビター、抑制物質

関: blocker、depressant、suppressant

「activator」

　　[★]

n.

活性化因子、活性化薬、活性化剤、賦活薬、活性化物質、アクチベーター、アクティベーター

「plasminogen activator」

　　[★] プラスミノーゲンアクチベーター, PA

[1] Elokdah H, Abou-Gharbia M, Hennan JK, et al. (July 2004). "Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization". J. Med. Chem. 47 (14): 3491–4. doi:10.1021/jm049766q. PMID 15214776.

[pmid11418606-2] Boncela, J; Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski C S (Sep. 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". J. Biol. Chem. (United States) 276 (38): 35305–11. doi:10.1074/jbc.M104028200. ISSN 0021-9258. PMID 11418606.

リンク元	「PAI-1」「プラスミノーゲンアクチベーターインヒビター1」
拡張検索	「plasminogen activator inhibitor 1 deficiency」「plasminogen activator inhibitor-1」
関連記事	「inhibit」「inhibitor」「activator」「plasminogen activator」

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案内

案内

plasminogen activator inhibitor 1