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dc.contributor.authorBudiono, Boris P
dc.contributor.authorHoe, Louise E See
dc.contributor.authorPeart, Jason N
dc.contributor.authorSabapathy, Surendran
dc.contributor.authorAshton, Kevin J
dc.contributor.authorHaseler, Luke J
dc.contributor.authorHeadrick, John P
dc.date.accessioned2017-05-03T13:17:45Z
dc.date.available2017-05-03T13:17:45Z
dc.date.issued2012
dc.date.modified2013-06-04T02:39:42Z
dc.identifier.issn0363-6119
dc.identifier.doi10.1152/ajpregu.00406.2011
dc.identifier.urihttp://hdl.handle.net/10072/47505
dc.description.abstractExercise triggers hormesis, conditioning hearts against damaging consequences of subsequent ischemia-reperfusion (I/R). We test whether "low-stress" voluntary activity modifies I/R tolerance and molecular determinants of cardiac survival. Male C57BL/6 mice were provided 7-day access to locked (7SED) or rotating (7EX) running-wheels before analysis of cardiac prosurvival (Akt, ERK 1/2) and prodeath (GSK3ߩ kinases, transcriptomic adaptations, and functional tolerance of isolated hearts to 25-min ischemia/45-min reperfusion. Over 7 days, 7EX mice increased running from 2.1 ᠰ.2 to 5.3 ᠰ.3 km/day (mean speed 38 ᠲ m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered 43 ᠳ% of ventricular force with diastolic contracture of 33 ᠳ mmHg, whereas 7EX hearts recovered 63 ᠵ% of force with diastolic dysfunction reduced to 23 ᠲ mmHg (P < 0.05). Cytosolic expression (total protein) of Akt and GSK3ߠwas unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts. Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3ߠphosphorylation increased ~90%. Microarray interrogation identified significant changes (=1.3-fold expression change, =5% FDR) in 142 known genes, the majority (92%) repressed. Significantly modified paths/networks related to inflammatory/immune function (particularly interferon-dependent), together with cell movement, growth, and death. Of only 14 induced transcripts, 3 encoded interrelated sarcomeric proteins titin, a-actinin, and myomesin-2, while transcripts for protective actin-stabilizing ND1-L and activator of mitochondrial biogenesis ALAS1 were also induced. There was no transcriptional evidence of oxidative heat-shock or other canonical "stress" responses. These data demonstrate that relatively brief voluntary activity substantially improves cardiac ischemic tolerance, an effect independent of shifts in Akt, but associated with increased total ERK 1/2 and phospho-inhibition of GSK3߮ Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in activity-dependent protection.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Physiological Society
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefromR1091
dc.relation.ispartofpagetoR1100
dc.relation.ispartofissue9
dc.relation.ispartofjournalAmerican Journal of Physiology – Regulatory, Integrative and Comparative Physiology
dc.relation.ispartofvolume302
dc.rights.retentionY
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchCardiology (incl. cardiovascular diseases)
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320101
dc.subject.fieldofresearchcode42
dc.titleVoluntary running in mice beneficially modulates myocardial ischemic tolerance, signaling kinases, and gene expression patterns
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorPeart, Jason N.
gro.griffith.authorSabapathy, Surendran


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