Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity

B P Budiono, Louise E. See Hoe, A R Brunt, Jason N. Peart, John P. Headrick, Luke J. Haseler

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

AIMS: We examined coupling of myocardial ischaemic tolerance to physical activity and inactivity, and whether this involves modulation of survival (AKT, AMPK, ERK1/2, HSP27, EGFR) and injury (GSK3β) proteins implicated in ischaemic preconditioning and calorie restriction.

METHODS: Proteomic modifications were assessed in ventricular myocardium, and tolerance to 25-min ischaemia in ex vivo perfused hearts from C57Bl/6 mice subjected to 14-day voluntary activity in running-naïve animals (Active); 7 days of subsequent inactivity (Inactive); brief (day 3) restoration of running (Re-Active); or time-matched inactivity.

RESULTS: Active mice increased running speed and distance by 75-150% over 14 days (to ~40 m min(-1) and 10 km day(-1) ), with Active hearts resistant to post-ischaemic dysfunction (40-50% improvements in ventricular pressure development, diastolic pressure and dP/dt). Cardioprotection was accompanied by ~twofold elevations in AKT, AMPK, HSP27 and GSK3β phosphorylation and EGFR expression. Ischaemic tolerance was reversed in Inactive hearts, paralleling reduced EGFR expression and GSK3β and ERK1/2 phosphorylation (AKT, AMPK, HSP27 phosphorylation unaltered). Running characteristics, ischaemic tolerance, EGFR expression and GSK3β phosphorylation returned to Active levels within 1-3 days of restored activity (without changes in AKT, AMPK or HSP27 phosphorylation). Transcriptional responses included activity-dependent Anp induction vs. Hmox1 and Sirt3 suppression, and inactivity-dependent Adora2b induction.

CONCLUSIONS: Data confirm the sensitive coupling of ischaemic tolerance to activity: voluntary running induces cardioprotection that dissipates within 1 week of inactivity yet recovers rapidly upon subsequent activity. While exercise in naïve animals induces a molecular profile characteristic of preconditioning/calorie restriction, only GSK3β and EGFR modulation consistently parallel activity- and inactivity-dependent ischaemic tolerance.

Original languageEnglish
Pages (from-to)112-122
Number of pages11
JournalActa Physiologica
Volume218
Issue number2
DOIs
Publication statusPublished - Oct 2016
Externally publishedYes

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AMP-Activated Protein Kinases
Running
Phosphorylation
Ischemic Preconditioning
Ventricular Pressure
Proteomics
Myocardium
Ischemia
Blood Pressure
Wounds and Injuries
Proteins

Cite this

Budiono, B. P., See Hoe, L. E., Brunt, A. R., Peart, J. N., Headrick, J. P., & Haseler, L. J. (2016). Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity. Acta Physiologica, 218(2), 112-122. https://doi.org/10.1111/apha.12710
Budiono, B P ; See Hoe, Louise E. ; Brunt, A R ; Peart, Jason N. ; Headrick, John P. ; Haseler, Luke J. / Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity. In: Acta Physiologica. 2016 ; Vol. 218, No. 2. pp. 112-122.
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Budiono, BP, See Hoe, LE, Brunt, AR, Peart, JN, Headrick, JP & Haseler, LJ 2016, 'Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity' Acta Physiologica, vol. 218, no. 2, pp. 112-122. https://doi.org/10.1111/apha.12710

Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity. / Budiono, B P; See Hoe, Louise E.; Brunt, A R; Peart, Jason N.; Headrick, John P.; Haseler, Luke J.

In: Acta Physiologica, Vol. 218, No. 2, 10.2016, p. 112-122.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity

AU - Budiono, B P

AU - See Hoe, Louise E.

AU - Brunt, A R

AU - Peart, Jason N.

AU - Headrick, John P.

AU - Haseler, Luke J.

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Budiono BP, See Hoe LE, Brunt AR, Peart JN, Headrick JP, Haseler LJ. Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity. Acta Physiologica. 2016 Oct;218(2):112-122. https://doi.org/10.1111/apha.12710