Ischemic preconditioning triggers tyrosine kinase signaling: a potential role for MAPKAP kinase 2

摘要: Myocardial adaptation to ischemia has been shown activate protein tyrosine kinase, potentiating activation of phospholipase D, which leads the stimulation mitogen-activated (MAP) kinases and MAP kinase-activated (MAPKAP) kinase 2. The present study sought further examine signal transduction pathway for MAPKAP 2 during ischemic adaptation. Isolated perfused rat hearts were adapted stress by repeated reperfusion. Hearts pretreated with genistein block whereas SB-203580 was used inhibit p38 kinases. Western blot analysis demonstrated that is phosphorylated Phosphorylation blocked genistein, suggesting mediated a signaling pathway. estimated following in vitro phosphorylation recombinant human heat shock 27 as specific substrate Again, both myocardial ischemia. Immunofluorescence microscopy anti-p38-antibody revealed primarily localized perinuclear regions. moves nucleus after After reperfusion, cytoplasmic striations myocytes become obvious, indicating translocation from cytoplasm. Corroborating these results, improved left ventricular functions reduced infarction reversed blocking either or kinase. These results demonstrate triggers kinase-regulated pathway, leading implicating role