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- Publisher Website: 10.1023/A:1021601512058
- Scopus: eid_2-s2.0-0037281357
- PMID: 12619887
- WOS: WOS:000179883900006
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Article: Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide
Title | Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide |
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Authors | |
Keywords | Ginkgo biloba leaf extract Macrophage Nitric oxide Nuclear factor kappa B Oxidative stress |
Issue Date | 2003 |
Citation | Molecular and Cellular Biochemistry, 2003, v. 243 n. 1-2, p. 37-47 How to Cite? |
Abstract | Hyperhomocysteinemia 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 Identifier | http://hdl.handle.net/10722/194400 |
ISSN | 2023 Impact Factor: 3.5 2023 SCImago Journal Rankings: 0.901 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Woo WH, CWH | - |
dc.contributor.author | Cheung, F | - |
dc.contributor.author | Chan, VWH | - |
dc.contributor.author | Siow, YL | - |
dc.contributor.author | O, K | - |
dc.date.accessioned | 2014-01-30T03:32:32Z | - |
dc.date.available | 2014-01-30T03:32:32Z | - |
dc.date.issued | 2003 | - |
dc.identifier.citation | Molecular and Cellular Biochemistry, 2003, v. 243 n. 1-2, p. 37-47 | - |
dc.identifier.issn | 0300-8177 | - |
dc.identifier.uri | http://hdl.handle.net/10722/194400 | - |
dc.description.abstract | Hyperhomocysteinemia 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.language | eng | - |
dc.relation.ispartof | Molecular and Cellular Biochemistry | - |
dc.subject | Ginkgo biloba leaf extract | - |
dc.subject | Macrophage | - |
dc.subject | Nitric oxide | - |
dc.subject | Nuclear factor kappa B | - |
dc.subject | Oxidative stress | - |
dc.title | Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: Antagonizing effect of ginkgolides and bilobalide | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1023/A:1021601512058 | - |
dc.identifier.pmid | 12619887 | - |
dc.identifier.scopus | eid_2-s2.0-0037281357 | - |
dc.identifier.volume | 243 | - |
dc.identifier.issue | 1-2 | - |
dc.identifier.spage | 37 | - |
dc.identifier.epage | 47 | - |
dc.identifier.isi | WOS:000179883900006 | - |
dc.identifier.issnl | 0300-8177 | - |