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

doi:10.1111/apha.12710

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

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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 language	English
Pages (from-to)	112-122
Number of pages	11
Journal	Acta Physiologica
Volume	218
Issue number	2
DOIs	https://doi.org/10.1111/apha.12710
Publication status	Published - Oct 2016
Externally published	Yes

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10.1111/apha.12710

Coupling of myocardial stress resistance and signalling to voluntary activity and inactivityAccepted author manuscript, 1.39 MBLicence: Other

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@article{1d3436e1f4824c2e81324bb7594a8d68,

title = "Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity",

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-na{\"i}ve 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 na{\"i}ve animals induces a molecular profile characteristic of preconditioning/calorie restriction, only GSK3β and EGFR modulation consistently parallel activity- and inactivity-dependent ischaemic tolerance.",

author = "Budiono, {B P} and {See Hoe}, {Louise E.} and Brunt, {A R} and Peart, {Jason N.} and Headrick, {John P.} and Haseler, {Luke J.}",

note = "{\textcopyright} 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.",

year = "2016",

month = oct,

doi = "10.1111/apha.12710",

language = "English",

volume = "218",

pages = "112--122",

journal = "Acta Physiologica",

issn = "1748-1708",

publisher = "Wiley Blackwell (American Society Bone & Mineral Research)",

number = "2",

}

TY - JOUR

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.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84986631563&partnerID=8YFLogxK

U2 - 10.1111/apha.12710

DO - 10.1111/apha.12710

M3 - Article

C2 - 27174591

SN - 1748-1708

VL - 218

SP - 112

EP - 122

JO - Acta Physiologica

JF - Acta Physiologica

IS - 2

ER -

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

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