Document Detail

Prostanoid production in Saccharomyces cerevisiae provides a novel assay for nonsteroidal anti-inflammatory drugs.
MedLine Citation:
PMID:  19207291     Owner:  NLM     Status:  MEDLINE    
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.
Maged E Mohamed; Colin M Lazarus
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-21
Journal Detail:
Title:  FEMS yeast research     Volume:  9     ISSN:  1567-1364     ISO Abbreviation:  FEMS Yeast Res.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101085384     Medline TA:  FEMS Yeast Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  420-7     Citation Subset:  IM    
School of Biological Sciences, University of Bristol, Bristol, UK.
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MeSH Terms
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
Models, Biological
Recombinant Proteins / biosynthesis,  genetics
Saccharomyces cerevisiae / genetics,  metabolism*
Thromboxane A2 / antagonists & inhibitors*,  biosynthesis
Thromboxane-A Synthase / biosynthesis,  genetics
Trypanosoma brucei brucei / genetics
Reg. No./Substance:
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; EC 2; EC 5.3.-/Intramolecular Oxidoreductases; EC synthetase; EC Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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