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Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool.

Wang W, Zhang H, Xue G, Zhang L, Zhang W, Wang L, Lu F, Li H, Bai S, Lin Y, Lou Y, Xu C, Zhao Y - Oxid Med Cell Longev (2014)

Bottom Line: However, IPC protection is ineffective in aged hearts.IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts.Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150086, China.

ABSTRACT

Background: Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.

Methods: Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.

Results: IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

Conclusion: Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

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Related in: MedlinePlus

Mitochondrial oxidative phosphorylation efficiency was evaluated based on mitochondrial state 3 and 4 oxygen consumption (a), the respiratory control rate (RCR) (b), the ADP/O ratio (the nanomoles of ADP phosphorylated by the nanomoles of O2) (c), and proton leakage (oligomycin-inhibited respiration) (d). Respiration was induced with pyruvate/malate (5 mM each) as energizing substrates and ADP (200 μM) to initiate state 3 respiration. Data are presented as the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the OPC group; #P < 0.05 versus the Ex-OPC group.
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fig4: Mitochondrial oxidative phosphorylation efficiency was evaluated based on mitochondrial state 3 and 4 oxygen consumption (a), the respiratory control rate (RCR) (b), the ADP/O ratio (the nanomoles of ADP phosphorylated by the nanomoles of O2) (c), and proton leakage (oligomycin-inhibited respiration) (d). Respiration was induced with pyruvate/malate (5 mM each) as energizing substrates and ADP (200 μM) to initiate state 3 respiration. Data are presented as the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the OPC group; #P < 0.05 versus the Ex-OPC group.

Mentions: We measured mitochondrial respiratory function, including the respiratory rates of states 3 and 4 (Figure 4(a)), the RCR (Figure 4(b)), the ADP/O ratio (Figure 4(c)), and proton leakage (Figure 4(d)) using pyruvate/malate as substrates. Mitochondrial proton leakage was measured as oligomycin-inhibited state 3 respiration, which was normalized to controls. We observed that the state 3 respiratory rate, RCR, and ADP/O ratio were significantly decreased and the proton leakage was significantly increased in the OIR group compared with the old control group (P < 0.05 for all). However, there were no significant differences in any of these indices between the OPC and OC groups. Interestingly, the state 3 respiratory rate, RCR, and ADP/O ratio were higher and the oxidative phosphorylation-independent proton leakage was lower in the exercised old preconditioned hearts than in the OPC hearts (P < 0.05 for all). However, these effects were significantly restrained in the DFMO-treated hearts, indicating that inhibiting polyamine synthesis decreased the efficiency of mitochondrial oxidative phosphorylation coupling. However, there were no significant differences in the mitochondrial state 4 respiratory rate among any of the experimental groups.


Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool.

Wang W, Zhang H, Xue G, Zhang L, Zhang W, Wang L, Lu F, Li H, Bai S, Lin Y, Lou Y, Xu C, Zhao Y - Oxid Med Cell Longev (2014)

Mitochondrial oxidative phosphorylation efficiency was evaluated based on mitochondrial state 3 and 4 oxygen consumption (a), the respiratory control rate (RCR) (b), the ADP/O ratio (the nanomoles of ADP phosphorylated by the nanomoles of O2) (c), and proton leakage (oligomycin-inhibited respiration) (d). Respiration was induced with pyruvate/malate (5 mM each) as energizing substrates and ADP (200 μM) to initiate state 3 respiration. Data are presented as the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the OPC group; #P < 0.05 versus the Ex-OPC group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4227379&req=5

fig4: Mitochondrial oxidative phosphorylation efficiency was evaluated based on mitochondrial state 3 and 4 oxygen consumption (a), the respiratory control rate (RCR) (b), the ADP/O ratio (the nanomoles of ADP phosphorylated by the nanomoles of O2) (c), and proton leakage (oligomycin-inhibited respiration) (d). Respiration was induced with pyruvate/malate (5 mM each) as energizing substrates and ADP (200 μM) to initiate state 3 respiration. Data are presented as the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the OPC group; #P < 0.05 versus the Ex-OPC group.
Mentions: We measured mitochondrial respiratory function, including the respiratory rates of states 3 and 4 (Figure 4(a)), the RCR (Figure 4(b)), the ADP/O ratio (Figure 4(c)), and proton leakage (Figure 4(d)) using pyruvate/malate as substrates. Mitochondrial proton leakage was measured as oligomycin-inhibited state 3 respiration, which was normalized to controls. We observed that the state 3 respiratory rate, RCR, and ADP/O ratio were significantly decreased and the proton leakage was significantly increased in the OIR group compared with the old control group (P < 0.05 for all). However, there were no significant differences in any of these indices between the OPC and OC groups. Interestingly, the state 3 respiratory rate, RCR, and ADP/O ratio were higher and the oxidative phosphorylation-independent proton leakage was lower in the exercised old preconditioned hearts than in the OPC hearts (P < 0.05 for all). However, these effects were significantly restrained in the DFMO-treated hearts, indicating that inhibiting polyamine synthesis decreased the efficiency of mitochondrial oxidative phosphorylation coupling. However, there were no significant differences in the mitochondrial state 4 respiratory rate among any of the experimental groups.

Bottom Line: However, IPC protection is ineffective in aged hearts.IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts.Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150086, China.

ABSTRACT

Background: Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.

Methods: Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.

Results: IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

Conclusion: Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

Show MeSH
Related in: MedlinePlus