| Cytochrome P450 2S1 Depletion Enhances Cell Proliferation and Migration in Bronchial Epithelial Cells, in part, through Modulation of Prostaglandin E2 Synthesis. | |
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MedLine Citation:
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PMID: 22863683 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cytochromes P450 (CYPs) contribute to the metabolic activation and inactivation of various endogenous substrates. Despite years of research, the physiological role of CYP2S1 remains unknown. Recently, CYP2S1 has demonstrated NADPH P450-reductase independent metabolism of cyclooxygenase (COX)-derived prostaglandins (e.g. Prostaglandin G2 (PGG2)) at nanomolar concentrations. Arachidonic acid is converted to prostaglandin precursors (PGG2 and PGH2), through COX. These precursors are used to synthesize numerous prostanoids, including PGE2. PGE2 promotes cell proliferation, cell migration, and inhibits apoptosis. CYP2S1 metabolism of PGG2 presumably sequesters PGG2 and PGH2, making them unavailable for synthesis of prostanoids like PGE2. Whether CYP2S1 contributes to prostaglandin metabolism and influences cell physiological remains to be determined. The purpose of this study was to evaluate the physiological role of CYP2S1, if any, in human bronchial epithelial cells (BEAS-2B). To do this, we used siRNA to deplete CYP2S1 mRNA and protein by approximately 75% and evaluated the impact of CYP2S1 depletion on cell proliferation and migration. CYP2S1 depletion enhanced both cell proliferation and migration in BEAS-2B. Consistent with the proposed role of CYP2S1 in PGE2 synthesis, the reduction in CYP2S1 expression doubled intracellular PGE2 levels. Interestingly, pharmacological administration of PGE2 enhanced cell proliferation in BEAS-2B cells but failed to promote migration. Our data reveal an important role for CYP2S1 in the regulation of cell proliferation and migration, occurring in part through modulation of prostaglandin synthesis. |
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Authors:
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Thushara W Madanayake; Trevor P Fidler; Theresa W Fresquez; Naing Bajaj; Aaron M Rowland |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-3 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: - ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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New Mexico State University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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