Genomes and Genes
Summary: Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
- Goetz S, Hellwege A, Stenzel I, Kutter C, Hauptmann V, Forner S, et al. Role of cis-12-oxo-phytodienoic acid in tomato embryo development. Plant Physiol. 2012;158:1715-27 pubmed publisher..These data suggest a role of OPDA or an OPDA-related compound for proper embryo development possibly by regulating carbohydrate supply and detoxification. ..
- Stojanovic I, Saksida T, Stosic Grujicic S. Beta cell function: the role of macrophage migration inhibitory factor. Immunol Res. 2012;52:81-8 pubmed publisher..This exceptionally versatile molecule regulates insulin secretion in physiological conditions, while in pathological states it alters beta cell function and induces their apoptosis or necrosis and affects beta cell neoplasia. ..
- Li J, Mo H, Xiong G, Zhang L, He J, Huang Z, et al. Tumor microenvironment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. J Biol Chem. 2012;287:35484-95 pubmed publisher..Taken together, our findings illustrate that tumor-derived MIF can affect patient prognosis, which might be related to the increase of Th17 cells in the NPC tumor microenvironment. ..
- Koga K, Kenessey A, Ojamaa K. Macrophage migration inhibitory factor antagonizes pressure overload-induced cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2013;304:H282-93 pubmed publisher..We conclude that MIF antagonizes myocardial hypertrophy and fibrosis in response to hemodynamic stress by maintaining a redox homeostatic phenotype and attenuating stress-induced activation of hypertrophic signaling pathways. ..
- Sjögren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S. Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci U S A. 2013;110:3806-11 pubmed publisher..We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based drug design. ..
- Facemire C, Griffiths R, Audoly L, Koller B, Coffman T. The impact of microsomal prostaglandin e synthase 1 on blood pressure is determined by genetic background. Hypertension. 2010;55:531-8 pubmed publisher..These data indicate that genetic background significantly modifies the BP response to mPGES1 deficiency. Exaggerated production of thromboxane may contribute to the robust hypertension and albuminuria in 129 mPGES1-deficient mice. ..
- Karagöz G, Duarte A, Ippel H, Uetrecht C, Sinnige T, van Rosmalen M, et al. N-terminal domain of human Hsp90 triggers binding to the cochaperone p23. Proc Natl Acad Sci U S A. 2011;108:580-5 pubmed publisher..We anticipate that our NMR approach has significant impact on future studies of full-length Hsp90 with cofactors and substrates, but also for the development of Hsp90 inhibiting anticancer drugs. ..
- Chang H, Meuillet E. Identification and development of mPGES-1 inhibitors: where we are at?. Future Med Chem. 2011;3:1909-34 pubmed publisher..This review summarizes the structures, and the in vitro and in vivo activities of these novel mPGES-1 inhibitors. Challenges that have been encountered are also discussed...
- Gosset M, Pigenet A, Salvat C, Berenbaum F, Jacques C. Inhibition of matrix metalloproteinase-3 and -13 synthesis induced by IL-1beta in chondrocytes from mice lacking microsomal prostaglandin E synthase-1. J Immunol. 2010;185:6244-52 pubmed publisher..These results demonstrate that PGE(2) plays a key role in the induction of MMP-3 and MMP-13 in an inflammatory context. Therefore, mPGES-1 could be considered as a critical target to counteract cartilage degradation in arthritis. ..
- Siemoneit U, Koeberle A, Rossi A, Dehm F, Verhoff M, Reckel S, et al. Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense. Br J Pharmacol. 2011;162:147-62 pubmed publisher..Suppression of PGE(2) formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties. ..
- Zhou Y, Shaw N, Li Y, Zhao Y, Zhang R, Liu Z. Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules. FASEB J. 2010;24:4668-77 pubmed publisher..Met64 seems to function as a kinetic clamp, pushing the thiol group of Cys65 close to the site of nucleophilic attack during catalysis. ..
- Cho Y, Crichlow G, Vermeire J, Leng L, Du X, Hodsdon M, et al. Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci U S A. 2010;107:11313-8 pubmed publisher..In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells. ..
- Akcali A, Pehlivan S, Pehlivan M, Sever T, Neyal M. Association of macrophage migration inhibitory factor gene promoter polymorphisms with multiple sclerosis in Turkish patients. J Int Med Res. 2010;38:69-77 pubmed..This study indicates that the MIF -173 CC genotype may cause susceptibility to multiple sclerosis in the white Turkish population and a younger age of disease onset is associated with this polymorphism. ..
- Nakanishi M, Gokhale V, Meuillet E, Rosenberg D. mPGES-1 as a target for cancer suppression: A comprehensive invited review "Phospholipase A2 and lipid mediators". Biochimie. 2010;92:660-4 pubmed publisher..The role of mPGES-1 in the pathogenesis of various cancers is discussed. In addition, an overview of recent efforts to develop small molecule inhibitors that target the protein with high selectivity is also be reviewed. ..
- Baron N, Deuster O, Noelker C, Stuer C, Strik H, Schaller C, et al. Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells. J Neurosci Res. 2011;89:711-7 pubmed publisher..These results underscore the importance of MIF in GBM and show that MIF and its receptors may be a promising target for the treatment of malignant gliomas. ..
- Lu D, Han C, Wu T. Microsomal prostaglandin E synthase-1 inhibits PTEN and promotes experimental cholangiocarcinogenesis and tumor progression. Gastroenterology. 2011;140:2084-94 pubmed publisher..mPGES-1 promotes experimental cholangiocarcinogenesis and tumor progression by inhibiting PTEN. ..
- Ikeda Matsuo Y, Hirayama Y, Ota A, Uematsu S, Akira S, Sasaki Y. Microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are both required for ischaemic excitotoxicity. Br J Pharmacol. 2010;159:1174-86 pubmed publisher..Microsomal prostaglandin E synthase-1 and COX-2 are co-induced by excess glutamate in ischaemic brain. These enzymes are co-localized and act together to exacerbate stroke injury, by excessive PGE(2) production...
- Liao B, Zhong B, Li Z, Tian X, Li Y, Li B. Macrophage migration inhibitory factor contributes angiogenesis by up-regulating IL-8 and correlates with poor prognosis of patients with primary nasopharyngeal carcinoma. J Surg Oncol. 2010;102:844-51 pubmed publisher..MIF may contribute to lymph node metastasis in NPC by inducing angiogenesis through the way of upregulation of IL-8 expression in an autocrine EBV-independent pathway. ..
- Chang H, Song Z, Wisner L, Tripp T, Gokhale V, Meuillet E. Identification of a novel class of anti-inflammatory compounds with anti-tumor activity in colorectal and lung cancers. Invest New Drugs. 2012;30:1865-77 pubmed publisher..p. of PGE0001 at 100 mg/kg decreases serum PGE(2) levels in mice within 5 h. In summary, our data suggest that the identified compound PGE0001 exerts anti-tumor activity via the inhibition of the PGE(2) synthesis pathway...
- Rörsch F, Wobst I, Zettl H, Schubert Zsilavecz M, Grosch S, Geisslinger G, et al. Nonacidic inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1) identified by a multistep virtual screening protocol. J Med Chem. 2010;53:911-5 pubmed publisher..Here, we present a successful virtual screening study that results in a potent nonacidic mPGES-1 inhibitor lacking COX inhibition...
- Terzuoli E, Donnini S, Giachetti A, Iñiguez M, Fresno M, Melillo G, et al. Inhibition of hypoxia inducible factor-1alpha by dihydroxyphenylethanol, a product from olive oil, blocks microsomal prostaglandin-E synthase-1/vascular endothelial growth factor expression and reduces tumor angiogenesis. Clin Cancer Res. 2010;16:4207-16 pubmed publisher..2-(3,4-dihydroxyphenil)-ethanol (DPE), a polyphenol present in olive oil, has been found to attenuate the growth of colon cancer cells, an effect presumably related to its anti-inflammatory activity...
- Schrader J, Deuster O, Rinn B, Schulz M, Kautz A, Dodel R, et al. Restoration of contact inhibition in human glioblastoma cell lines after MIF knockdown. BMC Cancer. 2009;9:464 pubmed publisher..Our study adds another puzzle stone to the role of MIF in tumor growth and progression by showing the importance of MIF for overcoming contact inhibition. ..
- Jernerén F, Eng F, Hamberg M, Oliw E. Linolenate 9R-dioxygenase and allene oxide synthase activities of Lasiodiplodia theobromae. Lipids. 2012;47:65-73 pubmed publisher..This strain also lacked the JA biosynthetic enzymes present in higher plants. ..
- Båge T, Kats A, Lopez B, Morgan G, Nilsson G, Burt I, et al. Expression of prostaglandin E synthases in periodontitis immunolocalization and cellular regulation. Am J Pathol. 2011;178:1676-88 pubmed publisher..These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE(2) production in the inflammatory condition periodontitis. ..
- De Simone R, Chini M, Bruno I, Riccio R, Mueller D, Werz O, et al. Structure-based discovery of inhibitors of microsomal prostaglandin E2 synthase-1, 5-lipoxygenase and 5-lipoxygenase-activating protein: promising hits for the development of new anti-inflammatory agents. J Med Chem. 2011;54:1565-75 pubmed publisher..2 ?M, (II) compound 20 that dually inhibits 5-lipoxygenase and mPGES-1, and (III) compound 7 apparently acting as 5-lipoxygenase-activating protein inhibitor (IC(50) = 0.4 ?M)...
- Gadjeva M, Nagashima J, Zaidi T, Mitchell R, Pier G. Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis. PLoS Pathog. 2010;6:e1000826 pubmed publisher..Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect. ..
- Guimarães M, de Aquino S, Coimbra L, Spolidorio L, Kirkwood K, Rossa C. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun. 2012;18:155-63 pubmed publisher..Curcumin potently inhibits innate immune responses associated with periodontal disease, suggesting a therapeutic potential in this chronic inflammatory condition. ..
- Mbalaviele G, Pauley A, Shaffer A, Zweifel B, Mathialagan S, Mnich S, et al. Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor. Biochem Pharmacol. 2010;79:1445-54 pubmed publisher..This profile of mPGES-1 inhibition, distinct from COX-2 inhibition in cells, validates mPGES-1 as an attractive target for therapeutic intervention...
- Jernerén F, Hoffmann I, Oliw E. Linoleate 9R-dioxygenase and allene oxide synthase activities of Aspergillus terreus. Arch Biochem Biophys. 2010;495:67-73 pubmed publisher..Our results demonstrate that linoleate 9R-dioxygenase linked to allene oxide synthase activities can be expressed in fungi. ..
- Dessein A, Stechly L, Jonckheere N, Dumont P, Monte D, Leteurtre E, et al. Autocrine induction of invasive and metastatic phenotypes by the MIF-CXCR4 axis in drug-resistant human colon cancer cells. Cancer Res. 2010;70:4644-54 pubmed publisher..Combination therapies targeting the CXCR4-MIF axis could potentially counteract the emergence of the invasive metastatic behavior in clonal derivatives of drug-resistant colon cancer cells. ..
- Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y, Murakami M. Prostaglandin E synthases: Understanding their pathophysiological roles through mouse genetic models. Biochimie. 2010;92:651-9 pubmed publisher..In this review, we summarize the current understanding of the in vivo roles of PGES enzymes by knockout mouse studies and provide an overview of their biochemical properties. ..
- Radmark O, Samuelsson B. Microsomal prostaglandin E synthase-1 and 5-lipoxygenase: potential drug targets in cancer. J Intern Med. 2010;268:5-14 pubmed publisher..Several compounds that target COX-2 or MPGES-1 also inhibit 5-lipoxygenase. This may be advantageous for treatment of some forms of cancer...
- Woods S, Bishop J. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter. Transgenic Res. 2011;20:421-8 pubmed publisher..We have used our system to over-express MYC in the melanocytic compartment and show for the first time that increased MYC expression can indeed promote melanocytic tumor formation. ..
- Lee J, Natsuizaka M, Ohashi S, Wong G, Takaoka M, Michaylira C, et al. Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis. Carcinogenesis. 2010;31:427-34 pubmed publisher..Thus, PTGES is a novel HIF-1alpha target gene, involved in prostaglandin E biosynthesis in the esophageal tumor hypoxic microenvironment, and this has implications in diverse tumors types, especially of squamous origin. ..
- Stumpe M, Gobel C, Faltin B, Beike A, Hause B, Himmelsbach K, et al. The moss Physcomitrella patens contains cyclopentenones but no jasmonates: mutations in allene oxide cyclase lead to reduced fertility and altered sporophyte morphology. New Phytol. 2010;188:740-9 pubmed publisher..Targeted knockout mutants for PpAOC1 and for PpAOC2 were generated, while double mutants could not be obtained. The ?PpAOC1 and ?PpAOC2 mutants showed reduced fertility, aberrant sporophyte morphology and interrupted sporogenesis. ..
- Merk M, Zierow S, Leng L, Das R, Du X, Schulte W, et al. The D-dopachrome tautomerase (DDT) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF). Proc Natl Acad Sci U S A. 2011;108:E577-85 pubmed publisher..These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology. ..
- de Oliveira Gomes A, de Oliveira Silva D, Silva N, de Freitas Barbosa B, Franco P, Angeloni M, et al. Effect of macrophage migration inhibitory factor (MIF) in human placental explants infected with Toxoplasma gondii depends on gestational age. Am J Pathol. 2011;178:2792-801 pubmed publisher..gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age. ..
- Sierro S, Donda A, Perret R, Guillaume P, Yagita H, Lévy F, et al. Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity. Eur J Immunol. 2011;41:2217-28 pubmed publisher..We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity. ..
- Guimaraes M, Coimbra L, de Aquino S, Spolidorio L, Kirkwood K, Rossa C. Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J Periodontal Res. 2011;46:269-79 pubmed publisher..Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression, but no studies have evaluated the effects of curcumin on periodontal disease in vivo...
- Shimura C, Satoh T, Igawa K, Aritake K, Urade Y, Nakamura M, et al. Dendritic cells express hematopoietic prostaglandin D synthase and function as a source of prostaglandin D2 in the skin. Am J Pathol. 2010;176:227-37 pubmed publisher..Thus, DCs could be an important source of skin PGD2 and may mediate or regulate skin inflammation by releasing PGD2 in response to various stimuli, contributing to the innate and/or acquired immune responses. ..
- Ikeda Matsuo Y, Tanji H, Ota A, Hirayama Y, Uematsu S, Akira S, et al. Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E2 EP3 receptors. Br J Pharmacol. 2010;160:847-59 pubmed publisher..Activity of mPGES-1 exacerbated stroke injury through EP(3) receptors and activation of Rho kinase and/or G(i). Thus, mPGES-1 and EP(3) receptors may be valuable therapeutic targets for treatment of human stroke. ..
- Hokari R, Kurihara C, Nagata N, Aritake K, Okada Y, Watanabe C, et al. Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis. Am J Physiol Gastrointest Liver Physiol. 2011;300:G401-8 pubmed publisher..An animal model study suggests that PGD(2) derived from L-PGDS-expressing cells plays proinflammatory roles in colitis. ..
- Ragolia L, Palaia T, Hall C, Klein J, Buyuk A. Diminished lipocalin-type prostaglandin D(2) synthase expression in human lung tumors. Lung Cancer. 2010;70:103-9 pubmed publisher..We conclude that L-PGDS may play a key role in modulating lung cancer growth and may offer a novel diagnostic and therapeutic approach for treatment. ..
- Christ A, Labzin L, Bourne G, Fukunishi H, Weber J, Sweet M, et al. Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D(2) synthases. J Med Chem. 2010;53:5536-48 pubmed publisher..Compound 34 therefore represents a selective hematopoietic prostaglandin D(2) synthase inhibitor. ..
- Dumitru C, Gholaman H, Trellakis S, Bruderek K, Dominas N, Gu X, et al. Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer. 2011;129:859-69 pubmed publisher..In conclusion, our data indicate that the effects of tumor-derived MIF on neutrophils represent an additional mechanism by which MIF might contribute to tumor progression. ..
- Gheorghe K, Thurlings R, Westman M, Boumans M, Malmstrom V, Trollmo C, et al. Prostaglandin E2 synthesizing enzymes in rheumatoid arthritis B cells and the effects of B cell depleting therapy on enzyme expression. PLoS ONE. 2011;6:e16378 pubmed publisher..Therefore we investigated the expression of PGE(2) pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue...
- Regis E, Barreto de Souza V, Morgado M, Bozza M, Leng L, Bucala R, et al. Elevated levels of macrophage migration inhibitory factor (MIF) in the plasma of HIV-1-infected patients and in HIV-1-infected cell cultures: a relevant role on viral replication. Virology. 2010;399:31-38 pubmed publisher..Our results show that HIV-1 induces MIF secretion and suggest that MIF influences the HIV-1 biology through activation of HIV-1 LTR. ..
- Tanaka H, Tsurumura T, Aritake K, Furubayashi N, Takahashi S, Yamanaka M, et al. Improvement in the quality of hematopoietic prostaglandin D synthase crystals in a microgravity environment. J Synchrotron Radiat. 2011;18:88-91 pubmed publisher..Most of the space-grown crystals showed better X-ray diffraction patterns than the terrestrially grown ones, indicating the advantage of a microgravity environment on protein crystallization, especially in the case of this protein. ..
- Donadio C. Serum and urinary markers of early impairment of GFR in chronic kidney disease patients: diagnostic accuracy of urinary ?-trace protein. Am J Physiol Renal Physiol. 2010;299:F1407-23 pubmed publisher..73 m(-2). In this selected group of CKD patients, the positive predictive value of urinary BTP for a GFR <90 ml·min(-1)·1.73 m(-2) was 85%, indicating that, in CKD patients, a urine-based test can predict a slight GFR impairment. ..
- Tseng C, Tzeng C, Shih P, Yang C, Chuang Y, Peng S, et al. Identification of furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives as orally active and selective inhibitors of microsomal prostaglandin E(2) synthase-1 (mPGES-1). Mol Divers. 2012;16:215-29 pubmed publisher..0 ?M. Therefore, compound 12 is a highly selective mPGES-1 inhibitor that can serve as a lead for the development of novel oral anti-inflammatory drug candidates. ..