title: Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion.
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.
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina. dvelez@ffyb.uba.ar.
authors.forename: Débora Elisabet
authors.initials: DE
authors.lastname: Vélez
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Hermann
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Mariángeles
authors.initials: M
authors.lastname: Barreda Frank
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Victoria Evangelina
authors.initials: VE
authors.lastname: Mestre Cordero
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Enrique Alberto
authors.initials: EA
authors.lastname: Savino
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Varela
authors.affiliation: Department of Biological Sciences, School of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Marina Prendes
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D051381:Rats; D015427:Reperfusion Injury; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002316:Cardiotonic Agents; D000077191:Wortmannin
keywords: Autophagy; Heart; Ischemia; PI3K; Preconditioning; Wortmannin