Abstract 17445: NF2 Regulates Mst1 Activation and Ischemia Reperfusion Injury

TL;DRAbstract

Neurofibromin 2 (NF2)/merlin is a tumor suppressor that can regulate activation of the hippo pathway in Drosophila and the mammalian liver, thereby inhibiting cell growth and promoting apoptosis. We have shown previously that the mammalian homologue of hippo, Mst1, has a similar function in the heart. Therefore, we sought to determine whether NF2 can mediate activation of Mst1 in the heart and modulate cardiac ischemia/reperfusion (I/R) injury. Both NF2 and Mst1 are activated by oxidative stress in isolated cardiomyocytes in vitro and in the heart following I/R. Increased expression of NF2 in cardiomyocytes increased Mst1 phosphorylation (2.9±0.2-fold vs LacZ, p<0.05) and elicited apoptosis (4.8±1.7-fold vs LacZ, p<0.05) that was prevented by co-expression of kinase inactive Mst1 (61±12% decrease vs. NF2, p<0.05). To examine the importance of endogenous NF2 in I/R injury, we employed two different genetic models - systemic heterozygous nf2 deletion ( nf2 +/- ) and cardiomyocyt

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