AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease

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dc.contributor.advisorHood, David A.
dc.creatorGreen, Alexander Edward
dc.date.accessioned2014-07-10T16:33:53Z
dc.date.available2014-07-10T16:33:53Z
dc.date.copyright2013-10-28
dc.date.issued2014-07-09
dc.date.updated2014-07-09T16:01:56Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractThere are multiple copies of mtDNA per cell and each mtDNA molecule contains the information to encode 13 electron transport chain (ETC) proteins. When mtDNA is depleted, there is a decrease in ETC activity. 5' AMP-activated protein kinase (AMPK) is a kinase that can initiate mitochondrial biogenesis and mitophagy. We hypothesized that treating cells harbouring low numbers of mtDNA with an AMPK activator (5-Aminoimidazole-4-carboxamide ribonucleoside; AICAR) would ameliorate the decrease in ETC activity and improve mtDNA copy number. We developed myoblasts (C2C12 cells) depleted of mtDNA with long-term ethidium bromide treatment. We treated selected clones for 24 hours with 1 mM AICAR to activate AMPK. AICAR treatment decreased markers of mitochondrial biogenesis, mitochondrial function (e.g. maximal cellular respiration), and mitochondrial degradation. Thus, failing to increase the energy producing capacity of the cell, activation of AMPK may have induced an energy sparing mechanism.en_US
dc.identifier.urihttp://hdl.handle.net/10315/27571
dc.language.isoenen_US
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectPhysiologyen_US
dc.subjectCellular biologyen_US
dc.subjectKinesiologyen_US
dc.subject.keywordsmtDNA depletion syndromeen_US
dc.subject.keywordsMitochondriaen_US
dc.subject.keywordsmtDNAen_US
dc.subject.keywordsAICARen_US
dc.subject.keywordsAMPKen_US
dc.subject.keywordsExerciseen_US
dc.subject.keywordsMitochondrial diseaseen_US
dc.subject.keywordsOxidative phosphorylationen_US
dc.subject.keywordsElectron transport chainen_US
dc.subject.keywordsETCen_US
dc.titleAMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Diseaseen_US
dc.typeElectronic Thesis or Dissertation

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