ORCID Profile
0000-0002-1189-739X
Current Organisation
Charles Sturt University
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Publisher: Wiley
Date: 15-06-2016
DOI: 10.1111/APHA.12710
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.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.YJMCC.2017.03.007
Abstract: Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort.
Publisher: American Physiological Society
Date: 05-2012
DOI: 10.1152/AJPREGU.00406.2011
Abstract: Exercise 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 (GSK3β) 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 ± 0.2 to 5.3 ± 0.3 km/day (mean speed 38 ± 2 m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered 43 ± 3% of ventricular force with diastolic contracture of 33 ± 3 mmHg, whereas 7EX hearts recovered 63 ± 5% of force with diastolic dysfunction reduced to 23 ± 2 mmHg ( P 0.05). Cytosolic expression (total protein) of Akt and GSK3β was unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts. Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3β phosphorylation 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, α-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 GSK3β. Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in activity-dependent protection.
Publisher: Public Library of Science (PLoS)
Date: 13-01-2022
DOI: 10.1371/JOURNAL.PONE.0261723
Abstract: Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a ergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT n = 6/group generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2% P .05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4% P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited ergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes ( Trim63 and Fbxo32 ), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in ergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading.
No related grants have been discovered for Boris Budiono.