| Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells. | |
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MedLine Citation:
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PMID: 1718438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipopolysaccharide (LPS) induced a time-dependent synthesis of nitric oxide (NO) in EMT6 adenocarcinoma cells, assayed by accumulation of NO-derived nitrite in the medium. The induction of NO synthesis was inhibited in a concentration-dependent manner by the glucocorticoids dexamethasone (IC50 = 5 nM) and hydrocortisone (IC50 = 20 nM) and this effect was partially antagonized by progesterone and cortexolone. If addition of dexamethasone was delayed 6 h or more, inhibition of nitrite accumulation over 24 h was substantially reduced, indicating a lack of direct effect of glucocorticoids on the NO synthase. Nitrite accumulation was accompanied by cell damage, which was increased by L-arginine and inhibited by NG-monomethyl-L-arginine (L-NMMA) and dexamethasone. These data show that NO is a primary cytotoxic mediator and that suppression of its formation by glucocorticoids explains some of their anti-inflammatory and cytoprotective effects. |
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Authors:
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K J O'Connor; S Moncada |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1097 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 1991 Oct |
Date Detail:
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Created Date: 1991-12-06 Completed Date: 1991-12-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 227-31 Citation Subset: IM |
Affiliation:
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Wellcome Research Laboratories, Beckenham, Kent, U.K. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Oxidoreductases
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biosynthesis* Arginine / analogs & derivatives, pharmacology Cell Survival / drug effects* Cortodoxone / pharmacology Dexamethasone / pharmacology* Enzyme Induction / drug effects Humans Hydrocortisone / pharmacology* Kinetics Lipopolysaccharides / metabolism Nitric Oxide / metabolism* Nitric Oxide Synthase Nitrites / analysis Progesterone / pharmacology Tumor Cells, Cultured omega-N-Methylarginine |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/Nitrites; 10102-43-9/Nitric Oxide; 152-58-9/Cortodoxone; 17035-90-4/omega-N-Methylarginine; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 57-83-0/Progesterone; 74-79-3/Arginine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.4.-/Amino Acid Oxidoreductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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