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Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion

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Abstract

Ischemic preconditioning (IPC) is one of the most powerful interventions to reduce ischemia-reperfusion injury. The aim of the present study was to investigate the involvement of the phosphatidylinositol-3-kinases (PI3Ks) family in cardioprotection exerted by IPC and the relationship between preservation of mitochondrial morphology and ATP synthesis capacity. In this regard, macroautophagy (autophagy) is considered a dynamic process involved in the replacement of aged or defective organelles under physiological conditions. IPC consisted of four 5-min cycles of ischemia-reperfusion followed by sustained ischemia. Wortmannin (W), a PI3K family inhibitor, was added to the perfusion medium to study the involvement of autophagy in the beneficial effects of IPC. In the present study, LC3-II/I expression was significantly increased in the IPC group when compared with the control group. The hearts subjected to IPC showed greater degradation of p62 than control groups, establishing the existence of an autophagic flow. Electron microscopy showed that IPC preserves the structural integrity of mitochondria after ischemia and at the end of reperfusion. Moreover, hearts subjected to IPC exhibited increased mitochondrial ATP synthesis. The beneficial effects of IPC were abolished by W in all trials of this study, abolishing the differences between the IPC and control groups. These results suggest that IPC could partly reduce injury by ischemia-reperfusion (I/R) by decreasing mitochondrial damage and promoting autophagy. Since W is a nonspecific inhibitor of the PI3Ks family, further research is required to confirm participation of PI3K in the response to IPC.

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Acknowledgments

The authors thank Norma Gladys Infante for technical assistance. This research was supported in part by grants from the University of Buenos Aires, the National Scientific and Technical Research Council (CONICET PIP 0774) and the Institute of Drug Chemistry and Metabolism (IQUIMEFA-CONICET).

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Authors and Affiliations

  1. Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina

    Débora Elisabet Vélez, Romina Hermann, Mariángeles Barreda Frank, Victoria Evangelina Mestre Cordero, Enrique Alberto Savino, Alicia Varela & Maria Gabriela Marina Prendes

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  1. Débora Elisabet Vélez
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  2. Romina Hermann
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  3. Mariángeles Barreda Frank
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  4. Victoria Evangelina Mestre Cordero
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  7. Maria Gabriela Marina Prendes
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Correspondence to Débora Elisabet Vélez.

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Vélez, D.E., Hermann, R., Frank, M.B. et al. Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion. J Physiol Biochem 72, 83–91 (2016). https://doi.org/10.1007/s13105-015-0460-6

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  • DOI: https://doi.org/10.1007/s13105-015-0460-6

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