Importance of phospho-GSK-3β in ischemic pre and postconditioning in SHR

MOSCA SM

Santiago

Congreso; XX Annual Meeting of the International Society for Heart Research Latin American Section; 2012

Sección Latinoamericana de la ISHR

P-GSK-3β mediates the cardioprotection achieved by ischemic pre (PRE)-and postconditioning (POS) in normotensive animals. Our aim was to determine the role played by that enzyme in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to 45 min global ischemia (GI) and 1 h reperfusion (R). In other groups a cycle of 5 min GI and 10 min of R was applied prior to 45 min-GI (PRE) or three cycles of 30 s-GI/30 s-R was applied at the start of R (POS). Other hearts received 3 mM LiCl – a GSK-3β inhibitor – 10 min before GI or during the first 3 min of R. Infarct size (IS) was determined by TTC staining. The expression of P-GSK-3β and P-Akt in cytosolic (cyt) and mitochondrial (m) fractions and P-GSK-3β/VDAC physical associations were assessed. The reduced glutathione (GSH) content, activity and expression of MnSOD and Ca2+-induced mPTP opening were also measured. IS was significantly diminished by PRE, POS and LiCl treatments. The cyt P-GSK-3β and P-Akt contents and physical associations decreased in IC hearts and were restored after interventions. The increases of cyt MnSOD activity and decreases of GSH content and mPTP opening of IC hearts were attenuated by the interventions. The results show that an attenuation of mPTP opening mediated by cyt P-GSK-3β/VDAC association is the main mechanism contributing to the reduction of IS and oxidative stress achieved by PRE and POS in SHR hearts.