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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

(a) Isolated cardiomyocytes were preloaded with DCFH-DA to measure ROS generation. (b) Statistical analysis of the average fluorescence intensity from the cardiomyocytes. The data shown are the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the IR group; #P < 0.05 versus exercised old PC group.
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fig6: (a) Isolated cardiomyocytes were preloaded with DCFH-DA to measure ROS generation. (b) Statistical analysis of the average fluorescence intensity from the cardiomyocytes. The data shown are the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the IR group; #P < 0.05 versus exercised old PC group.

Mentions: ROS levels were measured in isolated cardiomyocytes (Figures 6(a) and 6(b)). JC-1 staining was used to detect the ΔΨm of the isolated cardiomyocytes. The ratio of red and green fluorescence was used to represent the ΔΨm (Figures 7(a) and 7(b)). Carbonyl cyanide m-chlorophenyl hydrazone, the positive control, promoted mitochondrial inner membrane permeability, leading to dissipation of the H+ gradient across the inner mitochondrial membrane (Figure 7(c)). We found that IR caused a significant increase in ROS fluorescence and a significant decrease in ΔΨm in the cardiomyocytes from the YIR, OIR, and Ex-OIR groups compared with those from the YC, OC, and Ex-OC groups [ROS: 37.5 ± 4.3 (YIR) versus 9.8 ± 1.7 abs. units (YC); 42.1 ± 2.5 (OIR) versus 16.2 ± 4.6 abs. units (OC); and 43.8 ± 4.2 (Ex-IR) versus 17.3 ± 3.8 abs. units (Ex-C); ΔΨm: 0.31 ± 0.04 (YIR) versus 0.67 ± 0.05 (YC); 0.27 ± 0.06 (OIR) versus 0.46 ± 0.05 (OC); and 0.31 ± 0.06 (Ex-IR) versus 0.61 ± 0.05 (Ex-C), P < 0.05 for all]. In contrast, the ROS fluorescence was lower and the ΔΨm was higher in the PC cardiomyocytes isolated from the YPC and Ex-OPC hearts compared with those isolated from the YIR and Ex-OIR hearts [ROS: 11.8 ± 2.2 abs. units (YPC) versus YIR and 18.8 ± 2.0 abs. units (Ex-OPC) versus Ex-OIR; ΔΨm: 0.48 ± 0.02 (YPC) versus YIR and 0.46 ± 0.05 (Ex-OPC) versus Ex-OIR, P < 0.05 for all]. However, PC had a weaker influence on ROS levels and ΔΨm compared with the OIR group (OPC versus OIR, P > 0.05). Administering DFMO throughout PC cycles abolished the effect of exercise on the ROS fluorescence and ΔΨm in the Ex-OPC hearts. The concentration of ROS was increased to 47.8 ± 4.2 abs. units, and ΔΨm was decreased to 0.27 ± 0.04 (versus Ex-OPC, P < 0.05 for all).


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)

(a) Isolated cardiomyocytes were preloaded with DCFH-DA to measure ROS generation. (b) Statistical analysis of the average fluorescence intensity from the cardiomyocytes. The data shown are the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the IR group; #P < 0.05 versus exercised old PC group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4227379&req=5

fig6: (a) Isolated cardiomyocytes were preloaded with DCFH-DA to measure ROS generation. (b) Statistical analysis of the average fluorescence intensity from the cardiomyocytes. The data shown are the mean ± SE (n = 6 per group). *P < 0.05 versus the control group; †P < 0.05 versus the IR group; #P < 0.05 versus exercised old PC group.
Mentions: ROS levels were measured in isolated cardiomyocytes (Figures 6(a) and 6(b)). JC-1 staining was used to detect the ΔΨm of the isolated cardiomyocytes. The ratio of red and green fluorescence was used to represent the ΔΨm (Figures 7(a) and 7(b)). Carbonyl cyanide m-chlorophenyl hydrazone, the positive control, promoted mitochondrial inner membrane permeability, leading to dissipation of the H+ gradient across the inner mitochondrial membrane (Figure 7(c)). We found that IR caused a significant increase in ROS fluorescence and a significant decrease in ΔΨm in the cardiomyocytes from the YIR, OIR, and Ex-OIR groups compared with those from the YC, OC, and Ex-OC groups [ROS: 37.5 ± 4.3 (YIR) versus 9.8 ± 1.7 abs. units (YC); 42.1 ± 2.5 (OIR) versus 16.2 ± 4.6 abs. units (OC); and 43.8 ± 4.2 (Ex-IR) versus 17.3 ± 3.8 abs. units (Ex-C); ΔΨm: 0.31 ± 0.04 (YIR) versus 0.67 ± 0.05 (YC); 0.27 ± 0.06 (OIR) versus 0.46 ± 0.05 (OC); and 0.31 ± 0.06 (Ex-IR) versus 0.61 ± 0.05 (Ex-C), P < 0.05 for all]. In contrast, the ROS fluorescence was lower and the ΔΨm was higher in the PC cardiomyocytes isolated from the YPC and Ex-OPC hearts compared with those isolated from the YIR and Ex-OIR hearts [ROS: 11.8 ± 2.2 abs. units (YPC) versus YIR and 18.8 ± 2.0 abs. units (Ex-OPC) versus Ex-OIR; ΔΨm: 0.48 ± 0.02 (YPC) versus YIR and 0.46 ± 0.05 (Ex-OPC) versus Ex-OIR, P < 0.05 for all]. However, PC had a weaker influence on ROS levels and ΔΨm compared with the OIR group (OPC versus OIR, P > 0.05). Administering DFMO throughout PC cycles abolished the effect of exercise on the ROS fluorescence and ΔΨm in the Ex-OPC hearts. The concentration of ROS was increased to 47.8 ± 4.2 abs. units, and ΔΨm was decreased to 0.27 ± 0.04 (versus Ex-OPC, P < 0.05 for all).

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