日
関

WordNet

an enzyme that regulates prostaglandins that are important for the health of the stomach lining and kidneys; "an unfortunate side effect of NSAIDs is that they block Cox-1" (同)Cox-1
either of two related enzymes that control the production of prostaglandins and are blocked by aspirin (同)Cox

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/03 18:34:06」(JST)

wiki en

"COX-1" redirects here. COX-1 may also refer to mitochondrial cytochrome c oxidase subunit 1 (cox1).

Cyclooxygenase-1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene.^[1]^[2]

History

Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was purified more than 20 years ago and cloned in 1988.^[3]^[4]

Gene and isozymes

There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors.^[5] A splice variant of COX-1 termed COX-3 was identified in the CNS of dogs, but does not result in a functional protein in humans. Two smaller COX-1-derived proteins (the partial COX-1 proteins PCOX-1A and PCOX-1B) have also been discovered, but their precise roles are yet to be described.^[6]

Function

Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), is the key enzyme in prostaglandin biosynthesis. It converts free arachidonic acid, released from membrane phospholipids at the sn-2 ester binding site by the enzymatic activity of phospholipase A2, to prostaglandin (PG) H2. The reaction involves both cyclooxygenase (dioxygenase) and hydroperoxidase (peroxidase) activity. The cyclooxygenase activity incorporates two oxygen molecules into arachidonic acid or alternate polyunsaturated fatty acid substrates, such as linoleic acid and eicosapentaenoic acid. Metabolism of arachidonic acid forms a labile intermediate peroxide, PGG2, which is reduced to the corresponding alcohol, PGH2, by the enzyme’s hydroperoxidase activity. There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis.

While metabolizing arachidonic acid primarily to PGG2, COX-1 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE stereoisomers as well as a small amount of 11(R)-HETE.^[7] The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more impotantly, can be further metabolized to a major class of anti-inflammatory agents, the lipoxins.^[8] These alternate metabolites of COX-1 may contribute to its activities

COX-1 promotes the production of the natural mucus lining that protects the inner stomach and contributes to reduced acid secretion and reduced pepsin content.^[9]^[10] COX-1 is normally present in a variety of areas of the body, including not only the stomach but any site of inflammation.^[9]^[11]

Clinical significance

COX-1 is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. TXA2, the major product of COX-1 in platelets, induces platelet aggregation.^[12]^[13] Research has shown that the inhibition of COX-1 is sufficient to explain why aspirin is effective at reducing cardiac events.

References

^ Yokoyama C, Tanabe T (December 1989). "Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme". Biochem. Biophys. Res. Commun. 165 (2): 888–94. doi:10.1016/S0006-291X(89)80049-X. PMID 2512924.
^ Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (June 1991). "Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment". FASEB J. 5 (9): 2304–12. PMID 1907252.
^ Bakhle YS (1999). "Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors". Drugs Today 35 (4–5): 237–50. PMID 12973429.
^ Sakamoto C (October 1998). "Roles of COX-1 and COX-2 in gastrointestinal pathophysiology". J. Gastroenterol. 33 (5): 618–24. doi:10.1007/s005350050147. PMID 9773924.
^ "Entrez Gene: PTGS1 prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)".
^ Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (October 2002). "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13926–31. doi:10.1073/pnas.162468699. PMC 129799. PMID 12242329.
^ J. Lipid Res. 51:575-585, 2010
^ Prostaglandins Leukot. Essent. Fatty Acids 73:141-162, 2005
^ ^a ^b MedicineNet.com[Internet]. New York:WebMD. [updated 2003 March 3; cited 2010 February 1] Available from: http://www.medterms.com/script/main/art.asp?articlekey=7123
^ Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 661.
^ AWS-Law.com [Internet]. Florida. [cited 2010 February 1] Available from: http://www.aws-law.com/about.asp.
^ Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 1126.
^ Weitz Jeffrey I, "Chapter 112. Antiplatelet, Anticoagulant, and Fibrinolytic Drugs" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2891975.

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. アスピリンによる呼吸器疾患の増悪 aspirin exacerbated respiratory disease
2. 非ステロイド性抗炎症剤（NSAIDs）反応に対する診断上の課題および脱感作計画 diagnostic challenge and desensitization protocols for nsaid reactions
3. 血小板生物学 platelet biology
4. アデノウイルスの病因およびベクター使用 adenovirus pathogenesis and vector applications
5. COX-2選択的阻害剤の概要 overview of selective cox 2 inhibitors

English Journal

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

Fond G1, Hamdani N, Kapczinski F, Boukouaci W, Drancourt N, Dargel A, Oliveira J, Le Guen E, Marlinge E, Tamouza R, Leboyer M.Author information 1Pôle de psychiatrie des hôpitaux universitaires H Mondor, University Paris Est-Créteil, INSERM U955, Eq Psychiatrie Génétique, Fondation FondaMental Fondation de coopération scientifique en santé mentale, Créteil, France.AbstractOBJECTIVE: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders].
Acta psychiatrica Scandinavica.Acta Psychiatr Scand.2014 Mar;129(3):163-79. doi: 10.1111/acps.12211. Epub 2013 Nov 11.
OBJECTIVE: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders].METHOD: Four databases were explored, without any year or language restrictions. The ba
PMID 24215721

Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E2 Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway.

Bi Y1, Guo XK, Zhao H, Gao L, Wang L, Tang J, Feng WH.Author information 1State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.AbstractAtypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E2 (PGE2), synthesized by cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In this study, we found that PGE2, together with COX-1, was significantly elevated by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct binding of p-C/EBP-β to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-β remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV infection. Taken together, our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-β signaling pathway, resulting in the increase of PGE2, which might be the cause of high fever in infected pigs. Our findings might provide new insights into the molecular mechanisms underlying the pathogenesis of HP-PRRSV infection.
Journal of virology.J Virol.2014 Mar;88(5):2810-20. doi: 10.1128/JVI.03205-13. Epub 2013 Dec 18.
Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E2 (PGE2),
PMID 24352469

Synthetically modified bioisosteres of salicyl alcohol and their gastroulcerogenic assessment versus aspirin: biochemical and histological correlates.

Ali G1, Subhan F, Islam NU, Ullah N, Sewell RD, Shahid M, Khan I.Author information 1Department of Pharmacy, University of Peshawar, Peshawar, 25120, Pakistan.AbstractThe present study was conducted to synthesize nitrogen containing derivatives of salicyl alcohol and to investigate in vivo their ulcerogenic potential in comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4-iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-diium chloride (II)] were synthesized and their chemical structures were characterized using spectral data. In our previous study (Ali et al., Afr J Pharm Pharmacol 7:585-596, 2013), both compounds showed anti-inflammatory, antinociceptive, and antipyretic properties in standard animal models and a greater binding affinity for cyclooxygenase-2 versus cyclooxygenase-1 in molecular docking and dynamics analysis. For in vivo studies, animals were randomly divided into four groups. The synthetic compounds (both at 100 or 150 mg/kg), aspirin (150 mg/kg), or saline vehicle was administered orally, once daily for 6 days and then tested for ulcerogenic activity. At the end of the procedure, gastric juice and tissues were collected and subjected to biochemical and histological analyses. The results of the study revealed that in the case of the aspirin-treated group, there was a significant increase in gastric juice volume, free acidity, total acidity, and ulcer score and a decrease in gastric pH. Moreover, histological examination of the gastric mucosa of the aspirin-treated group indicated morphological changes while neither of the synthetic compounds showed any significant ulcerogenic or cytotoxic properties. The results of the present study suggest that both compounds are free from ulcerogenic side effects and may represent a better alternative to aspirin.
Naunyn-Schmiedeberg's archives of pharmacology.Naunyn Schmiedebergs Arch Pharmacol.2014 Mar;387(3):281-90. doi: 10.1007/s00210-013-0941-5. Epub 2013 Nov 29.
The present study was conducted to synthesize nitrogen containing derivatives of salicyl alcohol and to investigate in vivo their ulcerogenic potential in comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4-iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-dii
PMID 24292286

Japanese Journal

Altered gene expression profile in ovarian follicle in rats treated with indomethacin and RU486

Tsubota Kenjiro,Kanki Masayuki,Noto Takahisa [他],Nakatsuji Shunji,Oishi Yuji,Matsumoto Masahiro,Nakayama Hiroyuki
The Journal of Toxicological Sciences 40(3), 413-425, 2015
… It is well-known that indomethacin (the cyclooxygenase 1 & 2 inhibitor) and RU486 (or mifepristone, the progesterone receptor antagonist) block follicular rupture in rats. … In RU486-treated rats, Adamts1, Adamts9, Edn2, Ednra, Lyve1, Plat, and Pparg were down-regulated. …
NAID 130005068420

Chalcone Derivatives Inhibit Human Platelet Aggregation and Inhibit Growth in Human Bladder Cancer Cells

Wu Chien-Ming,Lin Kai-Wei,Teng Chi-Hung [他]
Biological & pharmaceutical bulletin 37(7), 1191–1198, 2014-07
NAID 40020103631

Antiplatelet Effects of Caffeic Acid Due to Ca2＋ MobilizationInhibition Via cAMP-Dependent Inositol-1, 4, 5-Trisphosphate Receptor Phosphorylation

Lee Dong-Ha,Kim Hyun-Hong,Cho Hyun-Jeong,Bae Jeong-Soo,Yu Young-Bin,Park Hwa-Jin
Journal of Atherosclerosis and Thrombosis 21(1), 23-37, 2014
… we investigated the effects of caffeic acid (CAFA), a phenolic acid, on Ca2＋-antagonistic cyclic nucleotides associated with the phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP) and the thromboxane A2 (TXA2)-associated microsomal cyclooxygenase-1 (COX-1) activity in collagen (10 μg/mL)-stimulated platelet aggregation.Methods: Washed platelets (108/mL) obtained from Sprague-Dawley rats (6-7 weeks old, male) …
NAID 130004845457

Related Pictures

★リンクテーブル★

リンク元	「シクロオキシゲナーゼ1」「シクロオキシゲナーゼ-1」
関連記事	「cyclooxygenase」

「シクロオキシゲナーゼ1」

Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)
	; PDB rendering based on 1diy.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1cqe, 1diy, 1ebv, 1eqg, 1eqh, 1fe2, 1ht5, 1ht8, 1igx, 1igz, 1pge, 1pgf, 1pgg, 1prh, 1pth, 1q4g, 1u67, 2ayl
Identifiers
Symbols	PTGS1 ; COX1; COX3; PCOX1; PES-1; PGG/HS; PGHS-1; PGHS1; PHS1; PTGHS
External IDs	OMIM: 176805 MGI: 97797 HomoloGene: 743 ChEMBL: 221 GeneCards: PTGS1 Gene
EC number	1.14.99.1
Gene ontology
Molecular function	• peroxidase activity; • prostaglandin-endoperoxide synthase activity; • heme binding; • metal ion binding; • dioxygenase activity;
Cellular component	• photoreceptor outer segment; • nucleus; • cytoplasm; • endoplasmic reticulum membrane; • intracellular membrane-bounded organelle;
Biological process	• prostaglandin biosynthetic process; • lipid metabolic process; • xenobiotic metabolic process; • response to oxidative stress; • regulation of blood pressure; • arachidonic acid metabolic process; • cyclooxygenase pathway; • regulation of cell proliferation; • small molecule metabolic process; • oxidation-reduction process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: cyclooxygenase-1
関: シクロオキシゲナーゼ-1

「シクロオキシゲナーゼ-1」

　　[★]

英: cyclooxygenase-1
関: シクロオキシゲナーゼ1

「cyclooxygenase」

　　[★] シクロオキシゲナーゼ　

[pmid2512924-1] Yokoyama C, Tanabe T (December 1989). "Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme". Biochem. Biophys. Res. Commun. 165 (2): 888–94. doi:10.1016/S0006-291X(89)80049-X. PMID 2512924.

[pmid1907252-2] Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (June 1991). "Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment". FASEB J. 5 (9): 2304–12. PMID 1907252.

[pmid12973429-3] Bakhle YS (1999). "Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors". Drugs Today 35 (4–5): 237–50. PMID 12973429.

[pmid9773924-4] Sakamoto C (October 1998). "Roles of COX-1 and COX-2 in gastrointestinal pathophysiology". J. Gastroenterol. 33 (5): 618–24. doi:10.1007/s005350050147. PMID 9773924.

[5] "Entrez Gene: PTGS1 prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)".

[CDRETES1-6] Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (October 2002). "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13926–31. doi:10.1073/pnas.162468699. PMC 129799. PMID 12242329.

[7] J. Lipid Res. 51:575-585, 2010

[8] Prostaglandins Leukot. Essent. Fatty Acids 73:141-162, 2005

[MedicineNetcomInternetNew-9] MedicineNet.com[Internet]. New York:WebMD. [updated 2003 March 3; cited 2010 February 1] Available from: http://www.medterms.com/script/main/art.asp?articlekey=7123

[10] Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 661.

[11] AWS-Law.com [Internet]. Florida. [cited 2010 February 1] Available from: http://www.aws-law.com/about.asp.

[12] Bruton LL, Lazo JS, Parker KL. Goodman & Gilman’s: the pharmacological basis of therapeutics. 11th edition. New York: McGraw-Hill; 2006. p. 1126.

[13] Weitz Jeffrey I, "Chapter 112. Antiplatelet, Anticoagulant, and Fibrinolytic Drugs" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2891975.

匿名

検索

案内

案内

cyclooxygenase-1