| Prostanoid production in Saccharomyces cerevisiae provides a novel assay for nonsteroidal anti-inflammatory drugs. | |
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MedLine Citation:
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PMID: 19207291 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prostanoids are a large family of lipid mediators originating from prostaglandin H synthase (PGHS) activity on the 20-carbon polyunsaturated fatty acids dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA) and eicosapentaenoic acid. The two mouse PGHS isoforms, PGHS-1 and PGHS-2, were expressed in Saccharomyces cerevisiae (yeast), as was a signal-peptide-deleted version of PGHS-1 (PGHS-1MA). PGHS-1 showed high activity with both AA and DGLA as substrate, whereas PGHS-2 activity was high with DGLA but low with AA. Signal peptide removal reduced the activity of PGHS-1MA by >50% relative to PGHS-1, but the residual activity indicated that correct targeting to the lumen of the endoplasmic reticulum may not be necessary for enzyme function. Coexpression of PGHS-1 with cDNAs encoding mouse prostaglandin I synthase and thromboxane A synthase, and with Trypanosoma brucei genomic DNA encoding prostaglandin F synthase in AA-supplemented yeast cultures resulted in production of the corresponding prostanoids, prostaglandin I(2), thromboxane A(2) and prostaglandin F(2alpha). The inhibitory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on prostanoid production were tested on yeast cells expressing PGHS-1 in AA-supplemented culture. Dose-dependent inhibition of prostaglandin H(2) production by aspirin, ibuprofen and indomethacin demonstrated the potential utility of this simple expression system in screening for novel NSAIDs. |
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Authors:
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Maged E Mohamed; Colin M Lazarus |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-21 |
Journal Detail:
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Title: FEMS yeast research Volume: 9 ISSN: 1567-1364 ISO Abbreviation: FEMS Yeast Res. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-05 Completed Date: 2009-07-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101085384 Medline TA: FEMS Yeast Res Country: England |
Other Details:
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Languages: eng Pagination: 420-7 Citation Subset: IM |
Affiliation:
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School of Biological Sciences, University of Bristol, Bristol, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents / pharmacology* Biosynthetic Pathways Cyclooxygenase 1 / biosynthesis, genetics Cyclooxygenase 2 / biosynthesis, genetics Cytochrome P-450 Enzyme System / biosynthesis, genetics Dinoprost / antagonists & inhibitors*, biosynthesis Drug Evaluation, Preclinical / methods* Epoprostenol / antagonists & inhibitors*, biosynthesis Intramolecular Oxidoreductases / biosynthesis, genetics Mice Models, Biological Recombinant Proteins / biosynthesis, genetics Saccharomyces cerevisiae / genetics, metabolism* Thromboxane A2 / antagonists & inhibitors*, biosynthesis Thromboxane-A Synthase / biosynthesis, genetics Trypanosoma brucei brucei / genetics |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Recombinant Proteins; 35121-78-9/Epoprostenol; 551-11-1/Dinoprost; 57576-52-0/Thromboxane A2; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.4/prostacyclin synthetase; EC 5.3.99.5/Thromboxane-A Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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