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Article: Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide

TitleHomocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide
Authors
Issue Date2003
Citation
Molecular and Cellular Biochemistry, 2003, v. 243 n. 1-2, p. 37-47 How to Cite?
AbstractHyperhomocysteinemia is an independent risk factor for atherosclerotic diseases. Inducible nitric oxide synthase (iNOS) is mainly expressed in macrophages upon stimulation. Overproduction of nitric oxide (NO) by iNOS can exacerbate the development of atherosclerosis. Our previous studies demonstrated that the extract of ginkgo biloba leaves (EGb) inhibited the iNOS-mediated NO production in monocyte-derived macrophage. We also reported that homocysteine could stimulate monocyte chemoattractant protein-1 (MCP-1) expression in vascular cells causing enhanced monocyte chemotaxis. The objective of the present study was to investigate the effect of homocysteine on iNOS-mediated NO production in macrophages and the antagonizing effect of EGb. Human monocytic cell (THP-1)-derived macrophages were incubated with homocysteine for various time periods. Homocysteine at concentrations of 0.05-0.1 mM significantly stimulated NO production and iNOS activity in macrophages via increased expression of iNOS mRNA and protein. The increased iNOS expression was associated with activation of nuclear factor-kappa B (NF-κB) arising from reduced expression of inhibitor protein (IκBα) mRNA as well as increased phosphorylation of IκBα protein in homocysteine-treated cells. EGb and its terpenoids (ginkgolide A, ginkgolide B and bilobalide) could antagonize the homocysteine effect on iNOS expression in macrophages via their antioxidant effect resulting in attenuation of NF-κB activation. Taken together, our results have demonstrated that homocysteine, at pathophysiological concentrations, stimulates iNOS-mediated NO production in macrophages. EGb and its terpenoids can antagonize such stimulatory effect via antioxidation and attenuation of NF-κB activation.
Persistent Identifierhttp://hdl.handle.net/10722/194400
ISSN
2015 Impact Factor: 2.613
2015 SCImago Journal Rankings: 1.019
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWoo WH, CWH-
dc.contributor.authorCheung, F-
dc.contributor.authorChan, VWH-
dc.contributor.authorSiow, YL-
dc.contributor.authorO, K-
dc.date.accessioned2014-01-30T03:32:32Z-
dc.date.available2014-01-30T03:32:32Z-
dc.date.issued2003-
dc.identifier.citationMolecular and Cellular Biochemistry, 2003, v. 243 n. 1-2, p. 37-47-
dc.identifier.issn0300-8177-
dc.identifier.urihttp://hdl.handle.net/10722/194400-
dc.description.abstractHyperhomocysteinemia is an independent risk factor for atherosclerotic diseases. Inducible nitric oxide synthase (iNOS) is mainly expressed in macrophages upon stimulation. Overproduction of nitric oxide (NO) by iNOS can exacerbate the development of atherosclerosis. Our previous studies demonstrated that the extract of ginkgo biloba leaves (EGb) inhibited the iNOS-mediated NO production in monocyte-derived macrophage. We also reported that homocysteine could stimulate monocyte chemoattractant protein-1 (MCP-1) expression in vascular cells causing enhanced monocyte chemotaxis. The objective of the present study was to investigate the effect of homocysteine on iNOS-mediated NO production in macrophages and the antagonizing effect of EGb. Human monocytic cell (THP-1)-derived macrophages were incubated with homocysteine for various time periods. Homocysteine at concentrations of 0.05-0.1 mM significantly stimulated NO production and iNOS activity in macrophages via increased expression of iNOS mRNA and protein. The increased iNOS expression was associated with activation of nuclear factor-kappa B (NF-κB) arising from reduced expression of inhibitor protein (IκBα) mRNA as well as increased phosphorylation of IκBα protein in homocysteine-treated cells. EGb and its terpenoids (ginkgolide A, ginkgolide B and bilobalide) could antagonize the homocysteine effect on iNOS expression in macrophages via their antioxidant effect resulting in attenuation of NF-κB activation. Taken together, our results have demonstrated that homocysteine, at pathophysiological concentrations, stimulates iNOS-mediated NO production in macrophages. EGb and its terpenoids can antagonize such stimulatory effect via antioxidation and attenuation of NF-κB activation.-
dc.languageeng-
dc.relation.ispartofMolecular and Cellular Biochemistry-
dc.titleHomocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1023/A:1021601512058-
dc.identifier.pmid12619887-
dc.identifier.scopuseid_2-s2.0-0037281357-
dc.identifier.volume243-
dc.identifier.issue1-2-
dc.identifier.spage37-
dc.identifier.epage47-
dc.identifier.isiWOS:000179883900006-

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