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dc.contributor.authorWendt, Lauren
dc.contributor.authorSee Hoe, Louise
dc.contributor.authorSachaphibulkij, Karishma
dc.contributor.authorDu Toit, Eugene
dc.contributor.authorPeart, Jason
dc.contributor.authorHeadrick, John
dc.description.abstractMitochondrial fission protein, dynamin-related protein-1 (DRP-1), may be a key determinant of cardiac resistance to ischemia-reperfusion (I-R) and other stresses. We examined the impact of I-R on myocardial expression of DRP-1 (together with Akt and Erk1/2), mitochondrial respiration, and injury in I-R hearts in 4mo male C57Bl/6 mice subject to DRP-1 inhibition. Functional recoveries of Langendorff perfused hearts subjected to 25 min ischemia/45 min reperfusion were significantly improved by pre-treatment with 1 µM MDIVI-1. Cell death (LDH efflux) was only modified by a higher 5 µM concentration. Protective effects were not replicated by an alternate inhibitor dynasore hydrate (1 µM). Ischemic insult repressed mitochondrial O2 consumption during early reperfusion, with a ~50% fall in complex I activity that was effectively reversed by MDIVI-1. Functional benefits were associated with MDIVI-1 dependent reductions in mitochondrial DRP-1 expression and cytosolic Erk1/2 phosphorylation during I-R, while phosphorylation of cardiac Akt was significantly augmented by MDIVI-1. A similar pattern was evident in parallel studies of H2O2 (400 µM) challenged H9c2 myoblasts, with MDIVI-1 negating oxidative-stress Erk1/2 phosphorylation whereas phosphoactivation of Akt was preserved. These data support a key role for DRP-1 in repressing I-R tolerance, mitochondrial function, and protective Akt phosphorylation (whilst also augmenting Erk1/2 activation). This role of DRP-1 in control of stress-resistance, mitochondrial function and survival-kinase signalling supports the potential value of targeting the protein to protect ischemic myocardium
dc.publisherThe FASEB Journal
dc.relation.ispartofconferencenameExperimental Biology
dc.relation.ispartofconferencetitleThe FASEB Journal
dc.relation.ispartoflocationBoston, USA
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.titleEffects of Dynamin-Related Protein-1 (DRP-1) Inhibition with MDIVI-1 on Myocardial Injury, Mitochondrial Respiration and Stress-Signalling in the Murine Heart
dc.typeConference output
dc.type.descriptionE3 - Conferences (Extract Paper)
dcterms.bibliographicCitationWendt, L, Effects of Dynamin-Related Protein-1 (DRP-1) Inhibition with MDIVI-1 on Myocardial Injury, Mitochondrial Respiration and Stress-Signalling in the Murine Heart, 2015, 29 (1_supplement)
gro.hasfulltextNo Full Text
gro.griffith.authorWendt, Lauren
gro.griffith.authorSee Hoe, Louise
gro.griffith.authorSachaphibulkij, Karishma
gro.griffith.authorDu Toit, Eugene
gro.griffith.authorPeart, Jason N.
gro.griffith.authorHeadrick, John P.
gro.griffith.authorHeadrick, Jonathon

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