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Article: Post-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Go6976 in murine microglia

TitlePost-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Go6976 in murine microglia
Authors
Issue Date2000
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/molbrainres
Citation
Molecular Brain Research, 2000, v. 79 n. 1-2, p. 18-31 How to Cite?
AbstractGlia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated post-transcriptionally through the destabilization of iNOS mRNA by the indolocarbazole compound, Go6976, in murine microglia. This Go6976 effect is specific for iNOS since tumor necrosis factor α was unaffected by the compound. Interestingly, the post-transcriptional effects ascribed to Go6976 were not observed with other inhibitors of protein kinase A, C (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect the iNOS/NO system at the transcriptional level. In the past, Go6976 has been reported to be a rather specific inhibitor of PKC in vitro. Results from our experiments, through prolonged treatment with phorbol esters and with the various PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest that the Go6976-mediated post-transcriptional regulation of iNOS gene expression and NO production in microglia is not mediated through its reputed effects on PKC activity. Since the effects of various neurotoxins and certain neurodegenerative diseases may be manifested through alterations in the iNOS/NO system, post-transcriptional control of this system may represent a novel strategy for therapeutic intervention. Copyright (C) 2000 Elsevier Science B.V.
Persistent Identifierhttp://hdl.handle.net/10722/149596
ISSN
2007 Impact Factor: 1.997
2008 SCImago Journal Rankings: 1.457
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJeohn, GHen_US
dc.contributor.authorChang, RCCen_US
dc.contributor.authorKim, WGen_US
dc.contributor.authorWilson, Ben_US
dc.contributor.authorMohney, RPen_US
dc.contributor.authorWetsel, WCen_US
dc.contributor.authorHong, JSen_US
dc.date.accessioned2012-06-26T05:55:42Z-
dc.date.available2012-06-26T05:55:42Z-
dc.date.issued2000en_US
dc.identifier.citationMolecular Brain Research, 2000, v. 79 n. 1-2, p. 18-31en_US
dc.identifier.issn0169-328Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/149596-
dc.description.abstractGlia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated post-transcriptionally through the destabilization of iNOS mRNA by the indolocarbazole compound, Go6976, in murine microglia. This Go6976 effect is specific for iNOS since tumor necrosis factor α was unaffected by the compound. Interestingly, the post-transcriptional effects ascribed to Go6976 were not observed with other inhibitors of protein kinase A, C (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect the iNOS/NO system at the transcriptional level. In the past, Go6976 has been reported to be a rather specific inhibitor of PKC in vitro. Results from our experiments, through prolonged treatment with phorbol esters and with the various PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest that the Go6976-mediated post-transcriptional regulation of iNOS gene expression and NO production in microglia is not mediated through its reputed effects on PKC activity. Since the effects of various neurotoxins and certain neurodegenerative diseases may be manifested through alterations in the iNOS/NO system, post-transcriptional control of this system may represent a novel strategy for therapeutic intervention. Copyright (C) 2000 Elsevier Science B.V.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/molbrainresen_US
dc.relation.ispartofMolecular Brain Researchen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBrain - Cytology - Enzymologyen_US
dc.subject.meshCarbazoles - Pharmacologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGene Expression Regulation, Enzymologic - Drug Effectsen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshLipopolysaccharides - Pharmacologyen_US
dc.subject.meshMiceen_US
dc.subject.meshNeuroglia - Cytology - Enzymologyen_US
dc.subject.meshNitric Oxide Synthase - Geneticsen_US
dc.subject.meshNitric Oxide Synthase Type Iien_US
dc.subject.meshProtein Kinase C - Metabolismen_US
dc.subject.meshProtein Kinase Inhibitorsen_US
dc.subject.meshRna Processing, Post-Transcriptional - Drug Effectsen_US
dc.subject.meshRna, Messenger - Geneticsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTetradecanoylphorbol Acetate - Pharmacologyen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.titlePost-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Go6976 in murine microgliaen_US
dc.typeArticleen_US
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_US
dc.identifier.authorityChang, RCC=rp00470en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0169-328X(00)00081-4en_US
dc.identifier.pmid10925140-
dc.identifier.scopuseid_2-s2.0-0034705457en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034705457&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume79en_US
dc.identifier.issue1-2en_US
dc.identifier.spage18en_US
dc.identifier.epage31en_US
dc.identifier.isiWOS:000088791000002-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridJeohn, GH=6602725495en_US
dc.identifier.scopusauthoridChang, RCC=7403713410en_US
dc.identifier.scopusauthoridKim, WG=7405813871en_US
dc.identifier.scopusauthoridWilson, B=35243580200en_US
dc.identifier.scopusauthoridMohney, RP=6603187076en_US
dc.identifier.scopusauthoridWetsel, WC=7006048597en_US
dc.identifier.scopusauthoridHong, JS=7404117981en_US

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