File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis

TitleGinsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis
Authors
KeywordsSignaling
PI3K/Akt
HIF-1α
Ginsenoside
Angiogenesis
Issue Date2011
PublisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0969-6970
Citation
Angiogenesis, 2011, v. 14 n. 4, p. 515-522 How to Cite?
AbstractHypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1alpha under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1alpha steady-state mRNA was not affected by Rg1. Rather, HIF-1alpha protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70(S6K)), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1alpha induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70(S6K) activities, respectively, resulted in diminished HIF-1alpha activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1alpha suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1alpha specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70(S6K). These results define a hypoxia-independent activation of HIF-1alpha, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling. © 2011 The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/144894
ISSN
2015 Impact Factor: 4.301
2015 SCImago Journal Rankings: 2.212
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKBU 1/06C
HKU
Funding Information:

This study was supported by grants from the Hong Kong Research Grant Council HKBU 1/06C and the HKU Outstanding Young Researcher Award to A.S.T.W.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorNg, HMen_HK
dc.contributor.authorTang, MKSen_HK
dc.contributor.authorWong, CCKen_HK
dc.contributor.authorWong, RNSen_HK
dc.contributor.authorWong, ASTen_HK
dc.date.accessioned2012-02-21T05:44:05Z-
dc.date.available2012-02-21T05:44:05Z-
dc.date.issued2011en_HK
dc.identifier.citationAngiogenesis, 2011, v. 14 n. 4, p. 515-522en_HK
dc.identifier.issn0969-6970en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144894-
dc.description.abstractHypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1alpha under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1alpha steady-state mRNA was not affected by Rg1. Rather, HIF-1alpha protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70(S6K)), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1alpha induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70(S6K) activities, respectively, resulted in diminished HIF-1alpha activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1alpha suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1alpha specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70(S6K). These results define a hypoxia-independent activation of HIF-1alpha, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling. © 2011 The Author(s).en_HK
dc.languageengen_US
dc.publisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0969-6970en_HK
dc.relation.ispartofAngiogenesisen_HK
dc.rightsThe original publication is available at www.springerlink.comen_US
dc.subjectSignalingen_HK
dc.subjectPI3K/Akten_HK
dc.subjectHIF-1αen_HK
dc.subjectGinsenosideen_HK
dc.subjectAngiogenesisen_HK
dc.subject.meshEndothelial Cells - metabolism-
dc.subject.meshGene Expression Regulation - drug effects-
dc.subject.meshGinsenosides - isolation and purification - pharmacology-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit - genetics - metabolism-
dc.subject.meshNeovascularization, Physiologic - physiology-
dc.subject.meshPanax - chemistry-
dc.titleGinsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4551/resserv?sid=springerlink&genre=article&atitle=Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis&title=Angiogenesis&issn=09696970&date=2011-12-01&volume=14&issue=4& spage=515&authors=Kar-Wah Leung, Hoi-Man Ng, Maggie K. S. Tang, <i>et al.</i>en_US
dc.identifier.emailLeung, KW: kwleung1@hku.hken_HK
dc.identifier.emailWong, AST: awong1@hku.hken_HK
dc.identifier.authorityLeung, KW=rp01674en_HK
dc.identifier.authorityWong, AST=rp00805en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1007/s10456-011-9235-zen_HK
dc.identifier.pmid21964931-
dc.identifier.pmcidPMC3214261-
dc.identifier.scopuseid_2-s2.0-84855198104en_HK
dc.identifier.hkuros203397-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855198104&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume14en_HK
dc.identifier.issue4en_HK
dc.identifier.spage515en_HK
dc.identifier.epage522en_HK
dc.identifier.eissn1573-7209en_US
dc.identifier.isiWOS:000297118800010-
dc.publisher.placeNetherlandsen_HK
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.relation.projectGinsenosides as functional ligands of steroid hormone receptors: from ligand-receptor interaction to cellular homeostasis-
dc.identifier.scopusauthoridWong, AST=23987963300en_HK
dc.identifier.scopusauthoridWong, RNS=7402126957en_HK
dc.identifier.scopusauthoridWong, CCK=54880371500en_HK
dc.identifier.scopusauthoridTang, MKS=16742726200en_HK
dc.identifier.scopusauthoridNg, HM=51864338400en_HK
dc.identifier.scopusauthoridLeung, KW=13106059300en_HK
dc.identifier.citeulike9883460-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats