| Inhibition of nitric oxide synthase gene expression in vivo and in vitro by repeated doses of endotoxin. | |
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MedLine Citation:
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PMID: 8897870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have examined the effects of repeated endotoxin administration in vivo and in vitro on the induction of nitric oxide synthase (NOS). In vivo, hepatic NOS activity and mRNA were increased markedly by the administration of Escherichia coli lipopolysaccharide (LPS). The change in hepatic NOS activity coincided with a marked accumulation of hepatic citrulline. Both enzyme activity and citrulline concentration returned to normal by 12 h after LPS administration. At this time, a subsequent administration of endotoxin caused no change in either NOS mRNA, NOS activity, or citrulline concentration, and thus an endotoxin-refractory state for nitric oxide (NO) synthesis was established. Normal sensitivity was reestablished by 24 h after the initial dose. In vitro studies using both a macrophage cell line (HD11) and primary macrophages indicated that LPS pretreatment caused cells in culture to become completely refractory to subsequent stimulation by LPS. Finally, we tested the hypothesis that NO may be involved in the development of the refractory state. Various inhibitors blocked the initial synthesis of NO by > 90% but failed to influence the development of the refractory state. Our study demonstrates both in vivo and in vitro that NO synthesis is completely blocked after repeated exposure to endotoxin by a mechanism that appears to be pretranslational. This model of early endotoxin tolerance may provide insight into the molecular mechanisms that regulate expression of the NOS gene. |
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Authors:
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C C Chang; C C McCormick; A W Lin; R R Dietert; Y J Sung |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 271 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1996 Oct |
Date Detail:
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Created Date: 1996-12-16 Completed Date: 1996-12-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: G539-48 Citation Subset: IM |
Affiliation:
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Division of Nutritional Sciences, Cornell University, Ithoca, New York 14853, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chickens Endotoxins / administration & dosage* Enzyme Induction / drug effects Gene Expression Regulation, Enzymologic Lipopolysaccharides / administration & dosage* Macrophages / metabolism Male Nitric Oxide Synthase / genetics* Nitrites / metabolism RNA, Messenger / genetics |
| Chemical | |
Reg. No./Substance:
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0/Endotoxins; 0/Lipopolysaccharides; 0/Nitrites; 0/RNA, Messenger; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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