title: Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
authors.forename: B P
authors.initials: BP
authors.lastname: Budiono
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
authors.forename: L E
authors.initials: LE
authors.lastname: See Hoe
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Brunt
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
authors.forename: J N
authors.initials: JN
authors.lastname: Peart
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia. j.headrick@griffith.edu.au.
authors.forename: J P
authors.initials: JP
authors.lastname: Headrick
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Haseler
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D031204:Caloric Restriction; D006321:Heart / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D017202:Myocardial Ischemia / Q000503:physiopathology; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*
keywords: cardioprotection; exercise; inactivity; ischaemia-reperfusion; survival kinase