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Ginseng (Panax quinquefolius) attenuates leptin-induced cardiac hypertrophy through inhibition of p115Rho guanine nucleotide exchange factor-RhoA-Rho- associated, coiled-coil containing protein kinase-dependent mitogen-activated protein kinase pathway act

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dc.contributor.author Moey M.
dc.contributor.author Rajapurohitam V.
dc.contributor.author Zeidan A.
dc.contributor.author Karmazyn M.
dc.contributor.editor
dc.date Dec-2011
dc.date.accessioned 2017-09-07T06:59:56Z
dc.date.available 2017-09-07T06:59:56Z
dc.date.issued 2011
dc.identifier 10.1124/jpet.111.182600
dc.identifier.isbn
dc.identifier.issn 00223565
dc.identifier.uri http://hdl.handle.net/10938/11214
dc.description.abstract Leptin is a 16-kDa peptide primarily derived from white adipocytes and is typically elevated in plasma of obese individuals. Although leptin plays a critical role in appetite regulation, leptin receptors have been identified in numerous tissues including the heart and have been shown to directly mediate cardiac hypertrophy through RhoA-ROCK (Ras homolog gene family, member A-Rho-associated, coiled-coil containing protein kinase)-dependent p38 mitogen-activated protein kinase (MAPK) activation; however, the basis for RhoA stimulation is unknown. Rho guanine nucleotide exchange factors (GEFs) catalyze the exchange of GDP for GTP resulting in Rho activation and may be the potential upstream factors mediating leptin-induced RhoA activation and therefore a potential target for inhibition. We investigated the effects of North American ginseng (Panax quinquefolius), reported to reduce cardiac hypertrophy, on RhoA-ROCK and MAPK activation in ventricular cardiomyocytes exposed to leptin (50 ng-ml) and the possible role of p115RhoGEF and p63RhoGEF in these responses. Leptin produced a robust hypertrophic response that was associated with RhoA-ROCK activation resulting in a significant increase in cofilin-2 phosphorylation and actin polymerization, the latter evidenced by a reduction in the G-F actin ratio. These effects were prevented by ginseng (10 μg-ml). The stimulation of RhoA-ROCK by leptin was associated with significantly increased p115RhoGEF gene and protein expression and exchange activity, all of which were completely prevented by ginseng. The ability of ginseng to prevent leptin-induced activation of RhoA-ROCK was further associated with diminished p38 MAPK activation and nuclear translocation. These results demonstrate a potent inhibitory effect of ginseng against leptin-induced cardiac hypertrophy, an effect associated with prevention of p115RhoGEF-RhoA-ROCK-dependent p38 MAPK activation. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
dc.format.extent
dc.format.extent Pages: (746-756)
dc.language English
dc.publisher BETHESDA
dc.relation.ispartof Publication Name: Journal of Pharmacology and Experimental Therapeutics; Publication Year: 2011; Volume: 339; no. 3; Pages: (746-756);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Ginseng (Panax quinquefolius) attenuates leptin-induced cardiac hypertrophy through inhibition of p115Rho guanine nucleotide exchange factor-RhoA-Rho- associated, coiled-coil containing protein kinase-dependent mitogen-activated protein kinase pathway act
dc.type Article
dc.contributor.affiliation Moey, M., Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
dc.contributor.affiliation Rajapurohitam, V., Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
dc.contributor.affiliation Zeidan, A., Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Karmazyn, M., Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
dc.contributor.authorAddress Karmazyn, M.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; email: Morris.Karmazyn@schulich.uwo.ca
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Anatomy, Cell Biology and Physiological Sciences;
dc.contributor.authorDepartment Anatomy, Cell Biology and Physiological Sciences
dc.contributor.authorDivision
dc.contributor.authorEmail Morris.Karmazyn@schulich.uwo.ca
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Moey, M
dc.contributor.authorInitials Rajapurohitam, V
dc.contributor.authorInitials Zeidan, A
dc.contributor.authorInitials Karmazyn, M
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress Karmazyn, M (reprint author), Univ Western Ontario, Dept Physiol and Pharmacol, Schulich Sch Med and Dent, London, ON N6A 5C1, Canada.
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 9
dc.description.citedTotWOSCount 9
dc.description.citedWOSCount 8
dc.format.extentCount 11
dc.identifier.articleNo
dc.identifier.coden JPETA
dc.identifier.pubmedID 21875949
dc.identifier.scopusID 81555204274
dc.identifier.url
dc.publisher.address 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
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dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr J. Pharmacol. Exp. Ther.
dc.relation.ispartOfIssue 3
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Journal of Pharmacology and Experimental Therapeutics
dc.relation.ispartofPubTitleAbbr J. Pharmacol. Exp. Ther.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 339
dc.source.ID WOS:000297267800002
dc.type.publication Journal
dc.subject.otherAuthKeyword
dc.subject.otherChemCAS Actins
dc.subject.otherChemCAS Cardiotonic Agents
dc.subject.otherChemCAS Cofilin 2
dc.subject.otherChemCAS Guanine Nucleotide Exchange Factors
dc.subject.otherChemCAS Leptin
dc.subject.otherChemCAS Mitogen-Activated Protein Kinases, 2.7.11.24
dc.subject.otherChemCAS Plant Extracts
dc.subject.otherChemCAS Receptors, Leptin
dc.subject.otherChemCAS p38 Mitogen-Activated Protein Kinases, 2.7.11.24
dc.subject.otherChemCAS rho guanine nucleotide exchange factors
dc.subject.otherChemCAS rho-Associated Kinases, 2.7.11.1
dc.subject.otherChemCAS rhoA GTP-Binding Protein, 3.6.5.2
dc.subject.otherIndex actin
dc.subject.otherIndex cardiac agent
dc.subject.otherIndex cofilin 2
dc.subject.otherIndex guanine nucleotide exchange factor
dc.subject.otherIndex leptin
dc.subject.otherIndex mitogen activated protein kinase p38
dc.subject.otherIndex p115Rho guanine nucleotide exchange factor
dc.subject.otherIndex p63Rho guanine nucleotide exchange factor
dc.subject.otherIndex Panax quinquefolius extract
dc.subject.otherIndex plant extract
dc.subject.otherIndex Rho kinase
dc.subject.otherIndex RhoA guanine nucleotide binding protein
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex actin polymerization
dc.subject.otherIndex animal cell
dc.subject.otherIndex article
dc.subject.otherIndex cell nucleus
dc.subject.otherIndex controlled study
dc.subject.otherIndex drug mechanism
dc.subject.otherIndex enzyme activation
dc.subject.otherIndex enzyme inhibition
dc.subject.otherIndex gene expression
dc.subject.otherIndex ginseng
dc.subject.otherIndex heart muscle cell
dc.subject.otherIndex heart ventricle hypertrophy
dc.subject.otherIndex newborn
dc.subject.otherIndex nonhuman
dc.subject.otherIndex panax quinquefolius
dc.subject.otherIndex priority journal
dc.subject.otherIndex protein expression
dc.subject.otherIndex protein function
dc.subject.otherIndex protein phosphorylation
dc.subject.otherIndex protein transport
dc.subject.otherIndex rat
dc.subject.otherIndex Actins
dc.subject.otherIndex Animals
dc.subject.otherIndex Cardiomegaly
dc.subject.otherIndex Cardiotonic Agents
dc.subject.otherIndex Cofilin 2
dc.subject.otherIndex Dose-Response Relationship, Drug
dc.subject.otherIndex Drug Evaluation, Preclinical
dc.subject.otherIndex Guanine Nucleotide Exchange Factors
dc.subject.otherIndex Heart Ventricles
dc.subject.otherIndex Humans
dc.subject.otherIndex Leptin
dc.subject.otherIndex Mitogen-Activated Protein Kinases
dc.subject.otherIndex Myocytes, Cardiac
dc.subject.otherIndex p38 Mitogen-Activated Protein Kinases
dc.subject.otherIndex Panax
dc.subject.otherIndex Phosphorylation
dc.subject.otherIndex Phytotherapy
dc.subject.otherIndex Plant Extracts
dc.subject.otherIndex Plant Roots
dc.subject.otherIndex Rats
dc.subject.otherIndex Rats, Sprague-Dawley
dc.subject.otherIndex Receptors, Leptin
dc.subject.otherIndex rho-Associated Kinases
dc.subject.otherIndex rhoA GTP-Binding Protein
dc.subject.otherKeywordPlus NEONATAL-RAT CARDIOMYOCYTES
dc.subject.otherKeywordPlus VENTRICULAR MYOCYTES
dc.subject.otherKeywordPlus ANGIOTENSIN-II
dc.subject.otherKeywordPlus HEART-FAILURE
dc.subject.otherKeywordPlus BLOOD-PRESSURE
dc.subject.otherKeywordPlus RHO-GTPASES
dc.subject.otherKeywordPlus RECEPTOR
dc.subject.otherKeywordPlus MONOCROTALINE
dc.subject.otherKeywordPlus ENDOTHELIN-1
dc.subject.otherKeywordPlus NHE-1
dc.subject.otherWOS Pharmacology and Pharmacy


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