Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10501
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dc.contributor.authorMount, Peter F-
dc.contributor.authorLane, Natalie-
dc.contributor.authorVenkatesan, Sudharsan-
dc.contributor.authorSteinberg, Gregory R-
dc.contributor.authorFraser, Scott A-
dc.contributor.authorKemp, Bruce E-
dc.contributor.authorPower, David Anthony-
dc.date.accessioned2015-05-15T23:57:58Z
dc.date.available2015-05-15T23:57:58Z
dc.date.issued2008-01-14-
dc.identifier.citationAtherosclerosis 2008en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/10501en
dc.description.abstractEndothelial cell lipotoxicity mediated by accumulation of free fatty acids is an early event in the pathogenesis of atherosclerosis. The energy-sensor AMP-activated protein kinase (AMPK) is a key regulator of endothelial cell lipid metabolism. To test the hypothesis that bradykinin (BK) regulates AMPK and fatty acid oxidation in endothelium, stimulations of bovine aortic endothelial cells (BAECs) with bradykinin were performed. BK stimulation caused a 2.3-fold increase in AMPK activity (p<0.05). Activation of AMPK by BK in BAECs was inhibited by STO-609, an inhibitor of calmodulin-dependent kinase kinase (CaMKK), which is a known kinase upstream of AMPK. BK stimulation of BAECs also increased phosphorylation of acetyl-CoA carboxylase and this was inhibited by both STO-609 and over expression of an adenovirus encoded AMPK dominant negative (Ad-AMPK-DN). Furthermore, BK caused a 1.7-fold increase in palmitate oxidation in BAECs (p<0.05) and this increase was completely inhibited by the Ad-AMPK-DN (p<0.005). Inhibition of AMPK activation in response to BK by STO-609 had no effect on activating phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser(1177), consistent with CaMKK and AMPK not being required for phosphorylation of eNOS in response to BK. In conclusion, BK stimulates endothelial cell fatty acid oxidation by CaMKK-dependent activation of AMPK. The effect of BK on endothelial lipid metabolism represents a novel pathway for targeting fatty acid mediated endothelial cell dysfunction.en_US
dc.language.isoenen
dc.subject.otherAMP-Activated Protein Kinasesen
dc.subject.otherAnimalsen
dc.subject.otherAorta.cytologyen
dc.subject.otherBradykinin.physiologyen
dc.subject.otherCalcium-Calmodulin-Dependent Protein Kinases.physiologyen
dc.subject.otherCattleen
dc.subject.otherCells, Cultureden
dc.subject.otherEndothelial Cells.physiologyen
dc.subject.otherFatty Acids.metabolismen
dc.subject.otherMetabolic Networks and Pathwaysen
dc.subject.otherMultienzyme Complexes.physiologyen
dc.subject.otherNitric Oxide Synthase Type III.metabolismen
dc.subject.otherOxidation-Reductionen
dc.subject.otherProtein-Serine-Threonine Kinases.physiologyen
dc.titleBradykinin stimulates endothelial cell fatty acid oxidation by CaMKK-dependent activation of AMPK.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleAtherosclerosisen_US
dc.identifier.affiliationNephrologyen_US
dc.identifier.doi10.1016/j.atherosclerosis.2007.12.003en_US
dc.description.pages28-36en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/18191860en
dc.type.contentTexten_US
dc.type.austinJournal Articleen
local.name.researcherMount, Peter F
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptNephrology-
crisitem.author.deptInstitute for Breathing and Sleep-
crisitem.author.deptMedicine (University of Melbourne)-
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