cGMP-dependent protein kinase type I inhibits TAB1-p38 mitogen-activated protein kinase apoptosis signaling in cardiac myocytes

摘要: Cardiac myocyte apoptosis during ischemia and reperfusion (I/R) is tightly controlled by a complex network of stress-responsive signaling pathways. One pro-apoptotic pathway involves the interaction scaffold protein TAB1 with p38 mitogen-activated kinase (p38 MAPK) leading to autophosphorylation activation MAPK. Conversely, NO its second messenger cGMP protect cardiac myocytes from I/R. We provide evidence that target cGMP-dependent type I (PKG I) interferes TAB1-p38 MAPK I/R injury. In isolated neonatal myocytes, PKG inhibited MAPK, phosphorylation, induced simulated During in vivo, mice myocyte-restricted deletion displayed more pronounced stronger phosphorylation myocardial area at risk apoptotic infarct border zone as compared wild-type littermates. Notably, adenoviral expression constitutively active mutant truncated N terminus(PKGI-DeltaN1-92) did not inhibit vitro, indicating terminus required. As shown co-immunoprecipitation experiments HEK293 cells, cGMP-activated I, but I-DeltaN1-92 or mutants carrying point mutations N-terminal leucine-isoleucine zipper, interacted prevented binding Together, our data identify novel between serves defense mechanism against