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dc.contributor.advisorKorthuis, Ronald J.eng
dc.contributor.authorGaskin, F. Spencer, 1978-eng
dc.date.issued2007eng
dc.date.submitted2007 Summereng
dc.description"August 2007"eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionVita.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2007.eng
dc.description.abstractWe have previously demonstrated that consuming ethanol (ethanol preconditioning or EPC) at low levels 24 hrs prior to ischemia/reperfusion (I/R) prevents postischemic leukocyte-endothelial cell adhesive interactions (LEI) by a mechanism that is initiated by nitric oxide (NO) formed by endothelial NO synthase (eNOS). Recent work indicates that: 1) ethanol increases the activity of 5'-AMP-activated protein kinase (AMPK), 2) AMPK phosphorylates eNOS at Ser1177, resulting in activation, 3) NO from eNOS can activate ATP-sensitive potassium channels (KATP), and 4) NO has been shown to induce heme oxygenase-1 (HO-1) protein expression. In light of these observations, we postulated that AMPK activation may trigger the development of an anti-inflammatory phenotype similar to that induced by antecedent ethanol ingestion, and that this effect was mediated by eNOS, KATP, and HO-1. C57BL/6J, eNOS-/-, AMPK[alpha]1-/-, and AMPK[alpha]2-/- mice were treated with EPC or the AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) 24 hrs prior to I/R (AICAR-PC) in the presence or absence of inhibitors of the proposed mediators. I/R induced a marked increase in LEI relative to sham control mice. The postischemic increase in LEI was prevented by preconditioning with AICAR 24 hrs prior to I/R. AICAR-PC appears to be mediated by eNOS, KATP, and HO, as it was ineffective at reducing LEI in the eNOS-/-, AMPK[alpha]1-/-, or AMPK[alpha]2-/- mice or wild-type mice treated with the inhibitors of the proposed mediators. Our results indicate that AMPK agonists produce an anti-inflammatory phenotype in postcapillary venules by an eNOS, KATP, and HO-dependent mechanism.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.identifier.merlinb66660579eng
dc.identifier.oclc316335034eng
dc.identifier.urihttps://doi.org/10.32469/10355/4805eng
dc.identifier.urihttps://hdl.handle.net/10355/4805
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subject.meshReperfusioneng
dc.subject.meshPotassium Channels -- metabolismeng
dc.subject.meshProtein Kinase Inhibitors -- pharmacologyeng
dc.subject.meshIschemia -- physiopathologyeng
dc.subject.meshNitric Oxide Synthase Type III -- metabolismeng
dc.subject.meshHeme Oxygenase-1 -- metabolismeng
dc.subject.meshInflammation -- prevention & controleng
dc.titleMechanisms of adenosine monophosphate-activated protein kinase-induced preconditioning in ischemia/reperfusioneng
dc.typeThesiseng
thesis.degree.disciplinePhysiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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