Genomes and Genes
Gene Symbol: Ptgs1
Description: prostaglandin-endoperoxide synthase 1
Alias: COX1, Cox-1, Cox-3, PGHS-1, PHS 1, Pghs1, prostaglandin G/H synthase 1, PGH synthase 1, cyclooxygenase-1, prostaglandin H2 synthase 1
- Langenbach R, Loftin C, Lee C, Tiano H. Cyclooxygenase-deficient mice. A summary of their characteristics and susceptibilities to inflammation and carcinogenesis. Ann N Y Acad Sci. 1999;889:52-61 pubmed..Furthermore, data from COX-deficient mice indicate that both isoforms can contribute to the inflammatory response and that both isoforms have significant roles in carcinogenesis. ..
- Gross G, Imamura T, Luedke C, Vogt S, Olson L, Nelson D, et al. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Proc Natl Acad Sci U S A. 1998;95:11875-9 pubmed..These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation. ..
- Kirtikara K, Morham S, Raghow R, Laulederkind S, Kanekura T, Goorha S, et al. Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. J Exp Med. 1998;187:517-23 pubmedProstaglandin E2 (PGE2) production in immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1-deficient (COX-1(-/-)) or cyclooxygenase 2-deficient (COX-2(-/-)) mice was examined after treatment with interleukin (IL)-..
- Langenbach R, Morham S, Tiano H, Loftin C, Ghanayem B, Chulada P, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. 1995;83:483-92 pubmed..To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1...
- Murakami M, Nakashima K, Kamei D, Masuda S, Ishikawa Y, Ishii T, et al. Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem. 2003;278:37937-47 pubmed..Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE2 involved in both tissue homeostasis and disease. ..
- Toscano C, Prabhu V, Langenbach R, Becker K, Bosetti F. Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain. Genome Biol. 2007;8:R14 pubmed
- Choi S, Langenbach R, Bosetti F. Cyclooxygenase-1 and -2 enzymes differentially regulate the brain upstream NF-kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis. J Neurochem. 2006;98:801-11 pubmed..Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca2+ -dependent PLA2, and terminal mPGES-2, to overcome defects in brain AA cascade. ..
- Kawada N, Solis G, Ivey N, Connors S, Dennehy K, Modlinger P, et al. Cyclooxygenase-1-deficient mice have high sleep-to-wake blood pressure ratios and renal vasoconstriction. Hypertension. 2005;45:1131-8 pubmed..COX-1 contributes to the normal nocturnal BP dipping phenomenon. ..
- Tiano H, Loftin C, Akunda J, Lee C, Spalding J, Sessoms A, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res. 2002;62:3395-401 pubmed..Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation. ..
- Chulada P, Thompson M, Mahler J, Doyle C, Gaul B, Lee C, et al. Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 2000;60:4705-8 pubmed..The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and that COX-1 may also be a chemotherapeutic target for nonsteroidal anti-inflammatory drugs. ..
- Morteau O, Morham S, Sellon R, Dieleman L, Langenbach R, Smithies O, et al. Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2. J Clin Invest. 2000;105:469-78 pubmed
- Francois H, Athirakul K, Mao L, Rockman H, Coffman T. Role for thromboxane receptors in angiotensin-II-induced hypertension. Hypertension. 2004;43:364-9 pubmed..However, irrespective of genetic background, the TP receptor makes a robust contribution to the pathogenesis of angiotensin II-dependent hypertension. ..
- Song W, Stubbe J, Ricciotti E, Alamuddin N, Ibrahim S, Crichton I, et al. Niacin and biosynthesis of PGD?by platelet COX-1 in mice and humans. J Clin Invest. 2012;122:1459-68 pubmed publisher..Thus, PGD?, like PGI?, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy. ..
- Wang H, Ma W, Tejada L, Zhang H, Morrow J, Das S, et al. Rescue of female infertility from the loss of cyclooxygenase-2 by compensatory up-regulation of cyclooxygenase-1 is a function of genetic makeup. J Biol Chem. 2004;279:10649-58 pubmed..We showed previously that targeted deletion of Ptgs2 encoding COX-2, but not Ptgs1 encoding COX-1, in C57BL/6J/129 mice produces complete female infertility resulting from multiple reproductive ..
- Kämpfer H, Bräutigam L, Geisslinger G, Pfeilschifter J, Frank S. Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003;120:880-90 pubmed..In contrast to the presence of an injury-induced cyclooxygenase-2, these data constitute strong evidence that cyclooxygenase-1-coupled prostaglandin E2/D2 biosynthesis has a central role in skin repair. ..
- Rocca B, Spain L, Pure E, Langenbach R, Patrono C, Fitzgerald G. Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development. J Clin Invest. 1999;103:1469-77 pubmed..COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development. ..
- Aid S, Silva A, Candelario Jalil E, Choi S, Rosenberg G, Bosetti F. Cyclooxygenase-1 and -2 differentially modulate lipopolysaccharide-induced blood-brain barrier disruption through matrix metalloproteinase activity. J Cereb Blood Flow Metab. 2010;30:370-80 pubmed publisher..Altogether, these results indicate that COX-2 activity modulates MMP-9 and-3 activities and is necessary to maintain BBB integrity during toll-like receptor 4-dependent innate immune activation. ..
- Chu X, Xu L, Nishimura K, Jisaka M, Nagaya T, Shono F, et al. Suppression of adipogenesis program in cultured preadipocytes transfected stably with cyclooxygenase isoforms. Biochim Biophys Acta. 2009;1791:273-80 pubmed publisher..Taken together, the results suggest that the sustained overexpression of either COX-1 or COX-2 resulted in the interference of adipogenesis program through a PG-independent mechanism with a different mode of action of COX isoforms. ..
- Swindle E, Coleman J, Deleo F, Metcalfe D. FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent. J Immunol. 2007;179:7059-71 pubmed
- Kraemer S, Meade E, DeWitt D. Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5'-flanking regulatory sequences. Arch Biochem Biophys. 1992;293:391-400 pubmed
- Blaho V, Buczynski M, Dennis E, Brown C. Cyclooxygenase-1 orchestrates germinal center formation and antibody class-switch via regulation of IL-17. J Immunol. 2009;183:5644-53 pubmed publisher..We conclude that IL-17 plays a role in Ab production and Ig class-switching in response to infection and that COX-1 is a critical, previously unrecognized regulator of this response. ..
- Suzuki Yamamoto T, Sugimoto Y, Ichikawa A, Ishimura K. Co-localization of prostaglandin F synthase, cyclooxygenase-1 and prostaglandin F receptor in mouse Leydig cells. Histochem Cell Biol. 2007;128:317-22 pubmed
- Kolaczkowska E, Goldys A, Kozakiewicz E, Lelito M, Plytycz B, Van Rooijen N, et al. Resident peritoneal macrophages and mast cells are important cellular sites of COX-1 and COX-2 activity during acute peritoneal inflammation. Arch Immunol Ther Exp (Warsz). 2009;57:459-66 pubmed publisher..The aim was thus to verify the expression and activity of the COX isoforms in resident peritoneal mast cells and macrophages during acute peritonitis...
- Zhang X, Morham S, Langenbach R, Young D. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med. 1999;190:451-59 pubmed..from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation...
- Frey M, Hilliard V, Mullane M, Polk D. ErbB4 promotes cyclooxygenase-2 expression and cell survival in colon epithelial cells. Lab Invest. 2010;90:1415-24 pubmed publisher..These results suggest that chronic overexpression of ErbB4 in the context of inflammation could contribute to colitis-associated tumorigenesis by inhibiting colonocyte apoptosis. ..
- Bethin K, Nagai Y, Sladek R, Asada M, Sadovsky Y, Hudson T, et al. Microarray analysis of uterine gene expression in mouse and human pregnancy. Mol Endocrinol. 2003;17:1454-69 pubmed
- Scotland R, Madhani M, Chauhan S, Moncada S, Andresen J, Nilsson H, et al. Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice: key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo. Circulation. 2005;111:796-803 pubmed..Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS-/-/COX-1-/- mice against hypertension. ..
- Sandee D, Sivanuntakorn S, Vichai V, Kramyu J, Kirtikara K. Up-regulation of microsomal prostaglandin E synthase-1 in COX-1 and COX-2 knock-out mouse fibroblast cell lines. Prostaglandins Other Lipid Mediat. 2009;88:111-6 pubmed publisher..Our earlier and the current studies demonstrate the coregulation of cPLA(2), COX, and mPGES-1, in PGE(2) synthesis pathway, and that these enzymes contribute to the elevation of PGE(2) level when one COX isoform is absent. ..
- Baumgartner H, Starodub O, Joehl J, Tackett L, Montrose M. Cyclooxygenase 1 is required for pH control at the mouse gastric surface. Gut. 2004;53:1751-7 pubmed..COX-1 is the dominant isoform regulating the normal thickness of the protective surface pH gradient in mouse stomach. ..
- Liu B, Zhang Y, Zhu N, Li H, Luo W, Zhou Y. A vasoconstrictor role for cyclooxygenase-1-mediated prostacyclin synthesis in mouse renal arteries. Am J Physiol Renal Physiol. 2013;305:F1315-22 pubmed publisher..Also, our data imply that endogenous COX-1-mediated PGI2 synthesis leads to vasoconstrictor activity and this could be an integral part of endothelium-derived mechanisms in regulating local renal vascular function. ..
- Xia Y, Bachinsky D, Smith J, McCluskey R, Warden C, Lusis A. Mapping of the glycoprotein 330 (Gp330) gene to mouse chromosome 2. Genomics. 1993;17:780-1 pubmed..We have mapped the Gp330 gene to mouse chromosome 2, 4.5 cM proximal to Acra, in an interspecific backcross of (C57BL/6J x Mus spretus) F1 x C57BL/6J. ..
- Church R, Jania L, Koller B. Prostaglandin E(2) produced by the lung augments the effector phase of allergic inflammation. J Immunol. 2012;188:4093-102 pubmed publisher..Together, this supports a model in which mPGES1-dependent PGE(2) produced by populations of cells native to the lung contributes to the effector phase of some allergic responses. ..
- Zha H, Remmers E, Du Y, Goldmuntz E, Mathern P, Zhang H, et al. A single linkage group comprising 11 polymorphic DNA markers on rat chromosome 3. Mamm Genome. 1994;5:538-41 pubmed..and four anonymous loci, formed a single linkage group covering approximately 112 cM with the following order: Ptgs1 (prostaglandin G/H synthase I)-D3Arb178-Scn2a (sodium channel, type II, alpha-polypeptide)-D3Arb1-Cat (catalase)-..
- Ansari H, Nadeem A, Tilley S, Mustafa S. Involvement of COX-1 in A3 adenosine receptor-mediated contraction through endothelium in mice aorta. Am J Physiol Heart Circ Physiol. 2007;293:H3448-55 pubmed..Expression of both A(3)AR and COX-1 was located mostly on endothelium of WT and A(3)KO +E aorta. These results demonstrate for the first time the involvement of COX-1 pathway in A(3)AR-mediated contraction via endothelium. ..
- Jiang Y, Yu V, Buchholz F, O Connell S, Rhodes S, Candeloro C, et al. A novel family of Cys-Cys, His-Cys zinc finger transcription factors expressed in developing nervous system and pituitary gland. J Biol Chem. 1996;271:10723-30 pubmed..Identification of a second mouse gene highly homologous to NZF-1, encoded by a distinct genomic locus, reveals a dispersed gene family encoding proteins containing Cys-Cys, His-Cys motifs. ..
- Li S, Ballou L, Morham S, Blatteis C. Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta. Brain Res. 2001;910:163-73 pubmed..c.v. PGE2 among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2 in response to pyrogens is critically dependent on COX-2 expression. ..
- Park J, Yang T, Arend L, Smart A, Schnermann J, Briggs J. Cyclooxygenase-2 is expressed in bladder during fetal development and stimulated by outlet obstruction. Am J Physiol. 1997;273:F538-44 pubmed..In regional bladder-distention models, COX-2 induction was confined to the area of distention. Bladder outlet obstruction stimulates COX-2 expression dramatically, reactivating a gene that is highly expressed during fetal development. ..
- Davis B, Lennard D, Lee C, Tiano H, Morham S, Wetsel W, et al. Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1beta. Endocrinology. 1999;140:2685-95 pubmed
- Zhang J, Goorha S, Raghow R, Ballou L. The tissue-specific, compensatory expression of cyclooxygenase-1 and -2 in transgenic mice. Prostaglandins Other Lipid Mediat. 2002;67:121-35 pubmed..These data suggest that expression of both COX-1 and COX-2 can be re-programmed to compensate for the lack of both alleles of the alternate COX gene in transgenic mice. ..
- Reese J, Binart N, Brown N, Ma W, Paria B, Das S, et al. Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR. Endocrinology. 2000;141:1872-81 pubmed..The function of uterine PRLR remains unclear. However, the eventual loss of pregnancy in P4-treated PRLR-/- mice suggests that uterine PRLR may be essential for the support of late gestation. ..
- Menon M, Tiedje C, Lafera J, Ronkina N, Konen T, Kotlyarov A, et al. Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNF? production. Biochem J. 2013;456:163-72 pubmed publisher..Interestingly, Ube2j1 is phosphorylated in response to LPS also in macrophages and contributes to MK2-dependent TNF? biosynthesis by a so far unknown mechanism. ..
- Muller Decker K, Furstenberger G. The cyclooxygenase-2-mediated prostaglandin signaling is causally related to epithelial carcinogenesis. Mol Carcinog. 2007;46:705-10 pubmed..Moreover, the COX-2 transgenic mouse lines are sensitized for cancer development. ..
- Li X, Mazaleuskaya L, Yuan C, Ballantyne L, Meng H, Smith W, et al. Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions. J Lipid Res. 2018;59:89-101 pubmed publisher..and their distinct roles, we have generated COX-2>COX-1 mice whereby Ptgs2 is knocked in to the Ptgs1 locus...
- Rouzer C, Tranguch S, Wang H, Zhang H, Dey S, Marnett L. Zymosan-induced glycerylprostaglandin and prostaglandin synthesis in resident peritoneal macrophages: roles of cyclo-oxygenase-1 and -2. Biochem J. 2006;399:91-9 pubmed..They also indicate that the 2-AG and AA used for PG-G and PG synthesis respectively are derived from independent pathways. ..
- Warden C, Davis R, Yoon M, Hui D, Svenson K, Xia Y, et al. Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase. J Lipid Res. 1993;34:1451-5 pubmed..Comparison of chromosomal locations for these genes in mouse and humans shows that the previously observed interspecies syntenies are preserved. ..
- Fornai M, Blandizzi C, Colucci R, Antonioli L, Bernardini N, Segnani C, et al. Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice. Gut. 2005;54:608-16 pubmed
- Wong W, Tian X, Chen Y, Leung F, Liu L, Lee H, et al. Bone morphogenic protein-4 impairs endothelial function through oxidative stress-dependent cyclooxygenase-2 upregulation: implications on hypertension. Circ Res. 2010;107:984-91 pubmed publisher..This BMP4/ROS/COX-2 cascade is important in the maintenance of endothelial dysfunction in hypertension. ..
- Gao Z, Zhang H, Liu J, Lau C, Liu P, Chen Z, et al. Cyclooxygenase-2-dependent oxidative stress mediates palmitate-induced impairment of endothelium-dependent relaxations in mouse arteries. Biochem Pharmacol. 2014;91:474-82 pubmed publisher..The present study provides novel evidence that palmitate up-regulates COX-2 through NF-ÎºB-dependent mechanism and resultant COX-2-associated oxidative stress impairs endothelium-dependent relaxations in mouse aortas. ..
- Aungier S, Ohmori H, Clinton M, Mabbott N. MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y. Immunology. 2015;144:34-44 pubmed publisher..the FDC-like cell line, FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line...
- Vogel C, Schuhmacher U, Degen G, Bolt H, Pineau T, Abel J. Modulation of prostaglandin H synthase-2 mRNA expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice. Arch Biochem Biophys. 1998;351:265-71 pubmed..These data suggest that the mechanism of modulation of both genes by TCDD may be different. ..
- Kuwamoto K, Miyauchi Hashimoto H, Tanaka K, Eguchi N, Inui T, Urade Y, et al. Possible involvement of enhanced prostaglandin E2 production in the photosensitivity in xeroderma pigmentosum group A model mice. J Invest Dermatol. 2000;114:241-6 pubmed..The induced production of PGE2 may be involved in the enhanced inflammation and immunosuppression caused by UV radiation in XPA-deficient mice and XP patients. ..
- Starodub O, Demitrack E, Baumgartner H, Montrose M. Disruption of the Cox-1 gene slows repair of microscopic lesions in the mouse gastric epithelium. Am J Physiol Cell Physiol. 2008;294:C223-32 pubmed..In conclusion, constitutive loss of Cox-1 leaves the gastric mucosa more prone to damage and slowed repair of microlesions. ..
- Houchen C, Stenson W, Cohn S. Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury. Am J Physiol Gastrointest Liver Physiol. 2000;279:G858-65 pubmed..These data suggest that prostaglandins synthesized by Cox-1 regulate multiple steps that determine the fate of crypt epithelial cell after genotoxic or cytotoxic injury...
- Bondesen B, Mills S, Kegley K, Pavlath G. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol Cell Physiol. 2004;287:C475-83 pubmed..Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease. ..
- Ayoub S, Botting R, Goorha S, Colville Nash P, Willoughby D, Ballou L. Acetaminophen-induced hypothermia in mice is mediated by a prostaglandin endoperoxide synthase 1 gene-derived protein. Proc Natl Acad Sci U S A. 2004;101:11165-9 pubmed..Thus, acetaminophen reduces basal body temperature below normal in mice most likely by inhibiting COX-3. ..
- Li S, Wang Y, Matsumura K, Ballou L, Morham S, Blatteis C. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(-/-), but not in cyclooxygenase-1(-/-) mice. Brain Res. 1999;825:86-94 pubmed..By contrast, COX-2+/- and COX-2-/- mice displayed no Tc rise after LPS. PFS did not affect the Tc of any animal. It would appear therefore that COX-2 is necessary for LPS-induced fever production. ..
- Armstrong P, Kirkby N, Chan M, Finsterbusch M, Hogg N, Nourshargh S, et al. Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction. Blood. 2015;126:e11-8 pubmed publisher..Such findings exemplify the value of screening platelet phenotypes of genetically modified mice and shed further light upon the roles and interactions of platelets in inflammation. ..
- Rouzer C, Kingsley P, Wang H, Zhang H, Morrow J, Dey S, et al. Cyclooxygenase-1-dependent prostaglandin synthesis modulates tumor necrosis factor-alpha secretion in lipopolysaccharide-challenged murine resident peritoneal macrophages. J Biol Chem. 2004;279:34256-68 pubmed..These results demonstrate autocrine regulation of TNF-alpha secretion by endogenous PGs synthesized primarily by COX-1 in RPM and suggest that COX-1 may play a significant role in the regulation of the early response to endotoxemia. ..
- Reddy S, Herschman H. Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells. J Biol Chem. 1997;272:3231-7 pubmed
- Saraswathi V, Ramnanan C, Wilks A, Desouza C, Eller A, Murali G, et al. Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice. Metabolism. 2013;62:1673-85 pubmed publisher..An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively. ..
- Ballou L, Botting R, Goorha S, Zhang J, Vane J. Nociception in cyclooxygenase isozyme-deficient mice. Proc Natl Acad Sci U S A. 2000;97:10272-6 pubmed..Thus, prostaglandins made by COX-1 mainly are involved in pain transmission in the stretching test in both male and female mice, whereas those made by COX-2 also may play a role in the stretching response in female mice. ..
- Russo I, Amornphimoltham P, Weigert R, Barlati S, Bosetti F. Cyclooxygenase-1 is involved in the inhibition of hippocampal neurogenesis after lipopolysaccharide-induced neuroinflammation. Cell Cycle. 2011;10:2568-73 pubmed..These results suggest that COX-1 may represent a viable therapeutic target to reduce neuroinflammation and promote neurogenesis in neurodegenerative diseases with a strong inflammatory component. ..
- Takahashi Y, Taketani Y, Endo T, Yamamoto S, Kumegawa M. Studies on the induction of cyclooxygenase isozymes by various prostaglandins in mouse osteoblastic cell line with reference to signal transduction pathways. Biochim Biophys Acta. 1994;1212:217-24 pubmed
- Yu Y, Fan J, Chen X, Wang D, Klein Szanto A, Campbell R, et al. Genetic model of selective COX2 inhibition reveals novel heterodimer signaling. Nat Med. 2006;12:699-704 pubmed..and analgesic actions of traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) while sparing the ability of PGHS1-derived prostaglandins to afford gastric cytoprotection...
- Widmer R, Engels M, Voss P, Grune T. Postanoxic damage of microglial cells is mediated by xanthine oxidase and cyclooxygenase. Free Radic Res. 2007;41:145-52 pubmed..Although, numerous free radical generating systems may contribute to the postanoxic microglial cell damage, the xanthine oxidase- and the cyclooxygenase-mediated oxidant production seems to be of major importance. ..
- Hilander T, Zhou X, Konovalova S, Zhang F, Euro L, Chilov D, et al. Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. Nucleic Acids Res. 2018;46:849-860 pubmed publisher..These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms. ..
- Sasso O, Migliore M, Habrant D, Armirotti A, Albani C, Summa M, et al. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. FASEB J. 2015;29:2616-27 pubmed publisher..Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive. ..
- Austin S, Funk C. Insight into prostaglandin, leukotriene, and other eicosanoid functions using mice with targeted gene disruptions. Prostaglandins Other Lipid Mediat. 1999;58:231-52 pubmed..g., receptors for various prostaglandins). This minireview will outline the phenotype of these knockout mice and what has been learned about eicosanoid functions through use of this novel methodology. ..
- Reddy S, Tiano H, Langenbach R, Morham S, Herschman H. Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells. Biochem Biophys Res Commun. 1999;265:205-10 pubmed..These data demonstrate that (i) the first phase of PG synthesis is COX-1 dependent and (ii) the second, delayed phase of PG synthesis is dependent on activation-induced synthesis and activity of COX-2. ..
- von Moltke J, Trinidad N, Moayeri M, Kintzer A, Wang S, Van Rooijen N, et al. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature. 2012;490:107-11 pubmed publisher..Our results therefore identify eicosanoids as a previously unrecognized cell-type-specific signalling output of the inflammasome with marked physiological consequences in vivo. ..
- Williams C, Tsujii M, Reese J, Dey S, DuBois R. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest. 2000;105:1589-94 pubmed..Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%. ..
- Ruud J, Nilsson A, Engström Ruud L, Wang W, Nilsberth C, Iresjö B, et al. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1. Brain Behav Immun. 2013;29:124-35 pubmed publisher..These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE(2) and neuronal EP(4) signaling...
- Skill N, Theodorakis N, Wang Y, Wu J, Redmond E, Sitzmann J. Role of cyclooxygenase isoforms in prostacyclin biosynthesis and murine prehepatic portal hypertension. Am J Physiol Gastrointest Liver Physiol. 2008;295:G953-64 pubmed publisher..Identification of additional target sites downstream of COX may benefit the >27,000 patients whom die annually from cirrhosis in the United States alone. ..
- Vennemann A, Gerstner A, Kern N, Ferreiros Bouzas N, Narumiya S, Maruyama T, et al. PTGS-2-PTGER2/4 signaling pathway partially protects from diabetogenic toxicity of streptozotocin in mice. Diabetes. 2012;61:1879-87 pubmed publisher..These findings offer the possibility to intervene in early progression of type 1 diabetes by using PTGER-selective agonists. ..
- Degousee N, Angoulvant D, Fazel S, Stefanski E, Saha S, Iliescu K, et al. c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2 synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1 expression and prostaglandin E2 biosynthesis by cardiomyocytes. J Biol Chem. 2006;281:16443-52 pubmed
- Myers L, Bhattacharya S, Herring P, Xing Z, Goorha S, Smith R, et al. The isozyme-specific effects of cyclooxygenase-deficiency on bone in mice. Bone. 2006;39:1048-1052 pubmed publisher..Further elucidation of the effects of the COX pathway on bone remodeling may provide important information on potential therapeutic targets for preventing and/or treating osteoporosis. ..
- Kojima F, Kapoor M, Yang L, Fleishaker E, Ward M, Monrad S, et al. Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice. J Immunol. 2008;180:8361-8 pubmed..Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. ..
- de Godoy M, Rattan N, Rattan S. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter. Am J Physiol Gastrointest Liver Physiol. 2009;296:G219-25 pubmed publisher..05, n = 5). However, basal tone in COX-2(-/-) mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone. ..