| Tobacco smoke regulates the expression and activity of microsomal prostaglandin E synthase-1: role of prostacyclin and NADPH-oxidase. | |
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MedLine Citation:
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PMID: 21737615 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tobacco smoke (TS) interacts with interleukin-1β (IL-1β) to modulate generation of reactive oxygen species (ROS) and expression of cyclooxygenase-2. We explored molecular mechanisms by which TS/IL-1β alters expression and activity of microsomal-prostaglandin E synthase-1 (mPGES-1) and of prostacyclin synthase (PGIS) in mouse cardiac endothelial cells. TS (EC(50) ∼5 puffs/L) interacting with IL-1β (2 μg/L) up-regulates PGE(2) production and mPGES-1 expression, reaching a plateau at 4-6 h, but down-regulates prostacyclin (PGI(2)) release by increasing IL-1β-mediated PGIS tyrosine nitration. Inhibition of NADPH-oxidase, achieved pharmacologically and/or by silencing its catalytic subunit p47phox, or exogenous PGI(2) (carbaprostacyclin; IC(50) ∼5 μM) prevents production of both ROS and PGE(2), and negatively modulates mPGES-1 expression induced by TS/IL-1β. Moreover, inhibiting PGI(2), either using PGIS siRNA and/or CAY10441 (EC(50) ∼20 nM), a PGI(2) receptor antagonist, increases NADPH-oxidase activation, mPGES-1 synthesis, and PGE(2) production. Finally, lower PGI(2) levels associated with higher PGIS tyrosine nitration, p47phox translocation to the membrane (an index of activation of NADPH-oxidase), and mPGES-1 expression and activity were detected in cardiovascular tissues of ApoE(-/-) mice exposed to cigarette smoke compared to control mice. In conclusion, cigarette smoke in association with cytokines alters the balance between PGI(2)/PGE(2), reducing PGI(2) production and increasing synthesis and activity of mPGES-1 via NADPH-oxidase activation, predisposing to development of pathological conditions. |
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Authors:
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Silvia S Barbieri; Patrizia Amadio; Sara Gianellini; Elena Zacchi; Babette B Weksler; Elena Tremoli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-07-07 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 25 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-03 Completed Date: 2011-12-07 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 3731-40 Citation Subset: IM |
Affiliation:
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Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milano, Italy. silviabarbieri@yahoo.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzyl Compounds / pharmacology Cell Line Endothelial Cells / drug effects Epoprostenol / analogs & derivatives, genetics, metabolism*, pharmacology Gene Expression Regulation, Enzymologic / drug effects* Imidazoles / pharmacology Interleukin-1beta / metabolism Intramolecular Oxidoreductases / genetics, metabolism* Male Mice NADPH Oxidase / genetics, metabolism* Reactive Oxygen Species / metabolism Smoke / adverse effects* Tobacco / adverse effects* |
| Chemical | |
Reg. No./Substance:
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0/(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); 0/Benzyl Compounds; 0/Imidazoles; 0/Interleukin-1beta; 0/Reactive Oxygen Species; 0/Smoke; 0/carbaprostacyclin; 35121-78-9/Epoprostenol; EC 1.6.3.1/NADPH Oxidase; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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