Abstract 14772: A Novel Role For Sphingosine Kinase-2 In PTP-mediated Cell Survival During Cardioprotection

Rationale: Although mitochondria are key determinants of myocardial injury during ischemia-reperfusion (I/R), their interaction with critical cytoprotective signaling systems is not fully understood. Activation of sphingosine kinase-1 protects the heart from I/R damage. A second isoform of sphingosine kinase, sphingosine kinase-2 (SphK2), was described in the regulation of complex IV assembly and mitochondrial respiration via interaction with mitochondrial prohibitin-2 (PHB2). Objective: In this study, we investigated the role of mitochondrial SphK2 in I/R injury. Methods and Results: Littermate (WT) and sphk2-/- mice underwent 45 minutes of in vivo ischemia and 24 hours reperfusion. Mice received no intervention (I/R) or preconditioning (PC) via 5 minutes I/R before the index ischemia. Despite the activation of PC-cytoprotective pathways (phosphorylation of ERK1/2, Akt, STAT3 and GSK3β) in both groups, infarct size in sphk2-/- mice was not reduced by PC (42±3 % PC vs. 43±4 % I/R, p=ns) vs. WT (24±3 % PC ...