2003. Role of 14-3-3-mediated p38 mitogen-activated protein kinase inhibition in cardiac myocyte survival

14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apo-ptotic, and checkpoint control pathways. Targeted ex-pression of dominant-negative 14-3-3 (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) activation. DN-14-3-3 mice are unable to compensate for pressure overload, which re-sults in increased mortality, dilated cardiomyopathy, and cardiac myocyte apoptosis. To evaluate the relative role of p38 MAPK activity in the DN-14-3-3 phenotype, we inhibited cardiac p38 MAPK activity by pharmacological and genetic methods. Intraperitoneal injection of SB202190, an inhibitor of p38 and p38 MAPK activ-ity, markedly increased the ability of DN-14-3-3 mice t