scholarly journals Structure of the human cyclo-oxygenase-2 gene

1994 ◽  
Vol 302 (3) ◽  
pp. 723-727 ◽  
Author(s):  
S B Appleby ◽  
A Ristimäki ◽  
K Neilson ◽  
K Narko ◽  
T Hla
Keyword(s):  
Genomic Library ◽  
Regulatory Sequences ◽  
Coding Region ◽  
Nf Kappa B ◽  
Protein Coding ◽  
Quiescent Cells ◽  
Cox 2 ◽  
Rate Limiting ◽  
Element Sequence ◽  
Cox 1

Cyclo-oxygenase (Cox), a rate-limiting enzyme in the synthesis of prostanoids, is encoded by two genes, Cox-1 and Cox-2, which are differentially expressed and regulated. Human Cox-1 and -2 polypeptides share 61% primary sequence identity. While the expression of Cox-1 is maximal in quiescent cells. Cox-2 expression is induced by growth factors and cytokines. We have screened a human genomic library with a probe from the 5′-untranslated region (UTR) of the human Cox-2 (hCox-2) cDNA and isolated two overlapping genomic clones. We have determined the DNA sequence of 0.8 kb upstream of the transcription start site, 6 kb of protein coding region, which includes 10 exons and 9 introns, as well as 2.5 kb of the 3′-UTR. The structures of the hCox-1 and hCox-2 and the murine TIS10 (Cox-2) genes are highly conserved, with a few exceptions. The 3′-UTRs of the Cox-1 and -2 genes are distinct; for example, the largest exon in the Cox-2 gene encodes the entire 3′-UTR, containing 22 copies of the ‘AUUUA’ RNA instability element. Sequence analysis of the 5′-flanking region has shown several potential transcription regulatory sequences, including a TATA box, a C/EBP motif, two AP-2 sites, three SP1 sites, two NF-kappa B sites, a CRE motif and an Ets-1 site. These efforts serve as a basis for future studies on transcriptional and post-transcriptional mechanisms of Cox-2 gene regulation.

Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids

1996 ◽  
Vol 16 (2) ◽  
pp. 107-122 ◽  
Author(s):  
I Chakraborty ◽  
S K Das ◽  
J Wang ◽  
S K Dey
Keyword(s):  
Vascular Permeability ◽  
Combined Treatment ◽  
Developmental Expression ◽  
Luminal Epithelium ◽  
Mouse Uterus ◽  
Ovarian Steroids ◽  
Ovariectomized Mice ◽  
Cox 2 ◽  
Rate Limiting ◽  
Cox 1

ABSTRACT Cyclo-oxygenase (COX) is a rate-limiting enzyme that converts arachidonic acid to prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In the rodent, increased uterine vascular permeability at sites of blastocyst apposition is one of the earliest prerequisite events in the implantation process. This event is preceded by generalized uterine edema and luminal closure, and coincides with the initial attachment reaction between the trophectoderm and luminal epithelium. Vasoactive PGs are implicated in these processes. Here we demonstrate that COX genes are differentially regulated in the peri-implantation mouse uterus. During the preimplantation period (days 1–4), the COX-1 gene was expressed in the uterine epithelium mainly on day 4 until the initiation of attachment reaction in the evening after which the expression was downregulated. This COX-1 expression coincides with the generalized uterine edema required for luminal closure. In contrast, the COX-2 gene was expressed in the luminal epithelium and subepithelial stromal cells at the anti-mesometrial pole exclusively surrounding the blastocyst at the time of attachment reaction on day 4 and persisted through the morning of day 5. This uterine gene was not expressed at the sites of blastocyst apposition during progesterone (P4) treated delayed implantation, but was readily induced in the uterus surrounding the activated blastocysts after termination of the delay by estradiol-17β (E2). The results suggest that PG synthesis catalyzed by COX-2 is important for localized increased uterine vascular permeability and attachment reaction. The COX-1 gene that was downregulated from the time of attachment reaction on day 4 was again expressed in the mesometrial and anti-mesometrial secondary decidual beds on days 7 and 8. These results suggest that PGs generated by COX-1 are involved in decidualization and/or continued localized endometrial vascular permeability observed during this period. In contrast, the COX-2 gene, expressed at the anti-mesometrial pole on days 4 and 5, switched its expression to the mesometrial pole from day 6 onward. These results suggest that PGs produced at this site by COX-2 are involved in angiogenesis for the establishment of placenta. In the ovariectomized mice, the COX-1 gene was induced in the epithelium by a combined treatment with P4 and E2. However, P4 and/or E2 treatments failed to influence the uterine COX-2 gene. Overall, the results suggest that the uterine COX-1 gene is influenced by ovarian steroids, while the COX-2 gene is regulated by the implanting blastocyst during early pregnancy.

scholarly journals Cyclooxygenases and prostaglandin E synthases in the endometrium of the rhesus monkey during the menstrual cycle

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 465-473 ◽  
Author(s):  
Tong Sun ◽  
Shi-Jie Li ◽  
Hong-Lu Diao ◽  
Chun-Bo Teng ◽  
Hong-Bin Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Menstrual Cycle ◽  
Rhesus Monkey ◽  
Luteal Phase ◽  
Glandular Epithelium ◽  
Prostaglandin E ◽  
Luminal Epithelium ◽  
Cox 2 ◽  
Rate Limiting ◽  
Cox 1

Cyclooxygenase (COX), a rate-limiting enzyme that produces prostaglandins (PGs) from arachidonic acid, exists in two isoforms, COX-1 and COX-2. PGE2 synthase (PGES) is a terminal prostanoid synthase and can enzymatically convert the cyclooxygenase product PGH2 to PGE2, including two isoforms: microsomal PGES (mPGES) and cytosolic PGES (cPGES). cPGES is predominantly linked with COX-1 to promote the immediate response. mPGES is preferentially coupled with the inducible COX-2 to promote delayed PGE2 generation. COX-2-deficient female mice are infertile with abnormalities in ovulation, fertilization, implantation and decidualization. The aim of this study was to examine immunohistochemically the expression pattern of COX-1, COX-2, mPGES and cPGES proteins in the endometrium of the rhesus monkey during the menstrual cycle. COX-1 immunostaining was mainly localized in the luminal epithelium and glandular epithelium near the lumen, and detected in all the stages during the menstrual cycle. COX-2 immunostaining was mainly localized in the luminal and glandular epithelium, and strongly shown during the mid-luteal phase (days 16 and 20) of the menstrual cycle. There was a strong cPGES immunostaining in the luminal and glandular epithelium on days 12, 16, 20 and 25 of the menstrual cycle. mPGES immunostaining was strongly detected in the glandular epithelium on days 20 and 25 of the menstrual cycle. These data suggest that the coupling of cPGES and COX-1 in the luminal epithelium may be responsible for the synthesis of PGE2 in monkey endometrium, and the coupling of mPGES and COX-2 in the glandular epithelium may be of importance for preparing the receptive endometrium.

scholarly journals The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies

2010 ◽  
Vol 2010 ◽  
pp. 1-21 ◽  
Author(s):  
Cyril Sobolewski ◽  
Claudia Cerella ◽  
Mario Dicato ◽  
Lina Ghibelli ◽  
Marc Diederich
Keyword(s):  
Cell Proliferation ◽  
Rate Limiting Step ◽  
Proliferation And Apoptosis ◽  
Cox 2 ◽  
Prostate Cancers ◽  
Cox 2 Inhibitors ◽  
Rate Limiting ◽  
Brain And Spinal Cord ◽  
Cox 1

It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. COX-2 modulation is a promising field investigated by many research groups.

scholarly journals Acidic Exopolysaccharide Produced from Marine Bacillus amyloliquefaciens 3MS 2017 for the Protection and Treatment of Breast Cancer

2020 ◽  
Vol 14 ◽  
pp. 117822342090207 ◽  
Author(s):  
Abeer Y Ibrahim ◽  
Eman R Youness ◽  
Manal G Mahmoud ◽  
Mohsen S Asker ◽  
Samah A El-Newary
Keyword(s):  
Breast Cancer ◽  
Growth Rate ◽  
Bacillus Amyloliquefaciens ◽  
Antioxidant Properties ◽  
Female Rats ◽  
Cancer Growth ◽  
Control Group ◽  
Cox 2 ◽  
Rate Limiting ◽  
Cox 1

Purpose: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine Bacillus amyloliquefaciens 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms. Methods: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA). B. amyloliquefaciens 3MS 2017 anti-breast-cancer property was evaluated by studying its effects on cancer-growth-rate-limiting enzymes (aromatase and Na+/K+ ATPase), sexual hormones (estrogen and progesterone), antioxidant and inflammatory biomarkers (cyclooxygenase-1; COX-1 and cyclooxygenase-2; COX-2). The incidence of breast cancer by DMBA was dependent on the level of carcinoembryonic antigen (CEA) and aromatase. Results: 7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na+/K+ ATPase subunits levels and CEA close to the normal level. Besides, BAEPS modulated a sexual hormone, in comparison with the cancer control group ( P ⩽ .05). B. amyloliquefaciens 3MS 2017 selectively inhibited COX-2 in parallel with promising antioxidant properties. The curative characters of BAEPS were more promising than the prophylactic. Conclusion: The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.

scholarly journals pgaA and pgaB encode two constitutively expressed endopolygalacturonases of Aspergillus niger

2000 ◽  
Vol 345 (3) ◽  
pp. 637-644 ◽  
Author(s):  
Lucie PAŘENICOVÁ ◽  
Jacques A. E. BENEN ◽  
Harry C. M. KESTER ◽  
Jaap VISSER
Keyword(s):  
Mode Of Action ◽  
Genomic Library ◽  
Degree Of Polymerization ◽  
Amino Acid Residues ◽  
Coding Region ◽  
Ph Optimum ◽  
Protein Coding ◽  
Standard Assay ◽  
Genes Encoding ◽  
Specific Mrna

pgaA and pgaB, two genes encoding endopolygalacturonases (PGs, EC 3.2.1.15) A and B, were isolated from a phage genomic library of Aspergillusniger N400. The 1167 bp protein coding region of the pgaA gene is interrupted by one intron, whereas the 1234 bp coding region of the pgaB gene contains two introns. The corresponding proteins, PGA and PGB, consist of 370 and 362 amino acid residues respectively. Northern-blot analysis revealed that pgaA- and pgaB-specific mRNA accumulate in mycelia grown on sucrose. mRNAs are also present upon transfer to media containing D-galacturonic acid and pectin. Recombinant PGA and PGB were characterized with respect to pH optimum, activity on polygalacturonic acid, and mode of action and kinetics on oligogalacturonates of different chain length (n = 3-7). At their pH optimum the specific activities in a standard assay for PGA (pH 4.2) and PGB (pH 5.0) were 16.5 μkat·mg-1 and 8.3 μkat·mg-1 respectively. Product progression analysis, using polygalacturonate as a substrate, revealed a random cleavage pattern for both enzymes and indicated processive behaviour for PGA. This result was confirmed by analysis of the mode of action using oligogalacturonates. Processivity was observed when the degree of polymerization of the substrate exceeded 6. Using pectins of various degrees of methyl esterification, it was shown that PGA and PGB both preferred partially methylated substrates.

scholarly journals Molecular Characterization of Feline COX-2 and Expression in Feline Mammary Carcinomas

2009 ◽  
Vol 46 (3) ◽  
pp. 423-429 ◽  
Author(s):  
K. Sayasith ◽  
J. Sirois ◽  
M. DorÉ
Keyword(s):  
Amino Acid ◽  
Molecular Characterization ◽  
Mammary Cancer ◽  
Immunohistochemical Analysis ◽  
Coding Region ◽  
Mammary Carcinomas ◽  
Acid Protein ◽  
Cox 2 ◽  
Rate Limiting

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the biosynthesis of prostaglandins, plays an important role in inflammation and tumorigenesis. COX-2 primary structure has been characterized in many species and its expression demonstrated in a variety of cancers in humans and dogs, including mammary cancer. In contrast, there is currently little information on the structure of feline COX-2. Also, information on COX-2 expression in feline mammary cancer is limited and conflicting. The objectives of this study were therefore to characterize the molecular structure of feline COX-2 and to evaluate by immunohistochemistry its expression in mammary carcinomas. Our results show that the predicted coding region of feline COX-2 encodes a 604-amino acid protein, which is identical in length to several COX-2 homologs. Feline COX-2 amino acid sequence is highly similar to other mammalian COX-2 homologs. Immunohistochemical analysis of 40 mammary carcinomas showed that the majority of tumors studied (35/40; 87%) expressed COX-2 at a level varying from low (20/40; 50%) to intermediate (13/40; 32%) and high (2/40; 5%). These results provide the first molecular characterization of feline COX-2 and demonstrate that COX-2 is expressed in the majority of feline mammary carcinomas.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Molecular Evolution at the decapentaplegic Locus in Drosophila

Genetics ◽  
1997 ◽  
Vol 145 (2) ◽  
pp. 297-309 ◽  
Author(s):  
Stuart J Newfeld ◽  
Richard W Padgett ◽  
Seth D Findley ◽  
Brent G Richter ◽  
Michele Sanicola ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Selective Constraint ◽  
Amino Acid Sequences ◽  
Regulatory Sequences ◽  
Protein Coding ◽  
Terminal Ligand ◽  
Cdna Sequences ◽  
Interspecific Comparisons

Using an elaborate set of cis-regulatory sequences, the decapentaplegic (dpp) gene displays a dynamic pattern of gene expression during development. The C-terminal portion of the DPP protein is processed to generate a secreted signaling molecule belonging to the transforming growth factor-β (TGF-β) family. This signal, the DPP ligand, is able to influence the developmental fates of responsive cells in a concentration-dependent fashion. Here we examine the sequence level organization of a significant portion of the dpp locus in Drosophila melanogaster and use interspecific comparisons with D. simulans, D. pseudoobscura and D.virilis to explore the molecular evolution of the gene. Our interspecific analysis identified significant selective constraint on both the nucleotide and amino acid sequences. As expected, interspecific comparison of protein coding sequences shows that the C-terminal ligand region is highly conserved. However, the central portion of the protein is also conserved, while the N-terminal third is quite variable. Comparison of noncoding regions reveals significant stretches of nucleotide identity in the 3′ untranslated portion of exon 3 and in the intron between exons 2 and 3. An examination of cDNA sequences representing five classes of dpp transcripts indicates that these transcripts encode the same polypeptide.

Selection on Rapidly Evolving Proteins in the Arabidopsis Genome

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 723-733 ◽  
Author(s):  
Marianne Barrier ◽  
Carlos D Bustamante ◽  
Jiaye Yu ◽  
Michael D Purugganan
Keyword(s):  
Expressed Sequence Tag ◽  
Amino Acid Replacement ◽  
Adaptive Divergence ◽  
Coding Region ◽  
Protein Coding ◽  
Hierarchical Bayesian Analysis ◽  
Brassicaceae Species ◽  
Replacement Site ◽  
Orthologous Loci ◽  
Selection Intensities

Abstract Genes that have undergone positive or diversifying selection are likely to be associated with adaptive divergence between species. One indicator of adaptive selection at the molecular level is an excess of amino acid replacement fixed differences per replacement site relative to the number of synonymous fixed differences per synonymous site (ω = Ka/Ks). We used an evolutionary expressed sequence tag (EST) approach to estimate the distribution of ω among 304 orthologous loci between Arabidopsis thaliana and A. lyrata to identify genes potentially involved in the adaptive divergence between these two Brassicaceae species. We find that 14 of 304 genes (∼5%) have an estimated ω > 1 and are candidates for genes with increased selection intensities. Molecular population genetic analyses of 6 of these rapidly evolving protein loci indicate that, despite their high levels of between-species nonsynonymous divergence, these genes do not have elevated levels of intraspecific replacement polymorphisms compared to previously studied genes. A hierarchical Bayesian analysis of protein-coding region evolution within and between species also indicates that the selection intensities of these genes are elevated compared to previously studied A. thaliana nuclear loci.

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