Document Detail

Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells.
MedLine Citation:
PMID:  1718438     Owner:  NLM     Status:  MEDLINE    
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.
K J O'Connor; S Moncada
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1097     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1991 Oct 
Date Detail:
Created Date:  1991-12-06     Completed Date:  1991-12-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  227-31     Citation Subset:  IM    
Wellcome Research Laboratories, Beckenham, Kent, U.K.
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MeSH Terms
Amino Acid Oxidoreductases / biosynthesis*
Arginine / analogs & derivatives,  pharmacology
Cell Survival / drug effects*
Cortodoxone / pharmacology
Dexamethasone / pharmacology*
Enzyme Induction / drug effects
Hydrocortisone / pharmacology*
Lipopolysaccharides / metabolism
Nitric Oxide / metabolism*
Nitric Oxide Synthase
Nitrites / analysis
Progesterone / pharmacology
Tumor Cells, Cultured
Reg. No./Substance:
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 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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