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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.date.accessioned2020-06-15T05:13:00Z
dc.date.available2020-06-15T05:13:00Z
dc.date.issued2015
dc.identifier.issn0892-6638
dc.identifier.doi10.1096/fasebj.29.1_supplement.1026.2
dc.identifier.urihttp://hdl.handle.net/10072/394649
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.ispartofdatefrom2015-03-28
dc.relation.ispartofdateto2015-04-01
dc.relation.ispartoflocationBoston, USA
dc.relation.ispartofissue1_supplement
dc.relation.ispartofvolume29
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchPhysiology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode110201
dc.subject.fieldofresearchcode1115
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0606
dc.subject.fieldofresearchcode1116
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)
dc.date.updated2020-06-15T04:35:00Z
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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