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p38 MITOGEN‐ACTIVATED PROTEIN KINASE (MAPK) IS ACTIVATED BY NORADRENALINE AND SERVES A CARDIOPROTECTIVE ROLE, WHEREAS ADRENALINE INDUCES p38 MAPK DEPHOSPHORYLATION
Author(s) -
Tsang Michael YC,
Rabkin Simon W
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05193.x
Subject(s) - dephosphorylation , mapk/erk pathway , p38 mitogen activated protein kinases , protein kinase a , kinase , programmed cell death , mitogen activated protein kinase , apoptosis , chemistry , microbiology and biotechnology , phosphorylation , fragmentation (computing) , biology , biochemistry , phosphatase , ecology
SUMMARY1 The aim of the present study was to investigate the role of p38 mitogen‐activated protein kinases (MAPK) in mediating the effect of noradrenaline (NA) on cardiomyocyte cell viability. 2 Cardiomyocytes from embryonic chick heart were treated with various concentrations of NA, phenylephrine or isoproterenol and p38 MAPK activation was determined by western blotting. Total cell death was assessed by the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay. Apoptosis was determined by specific DNA fragmentation. 3 At 100 µmol/L, NA produced a significant increase in cell death that was associated with microscopic changes and DNA fragmentation indicative of apoptosis. The p38 MAPK inhibitor SB202190 (at 1 µmol/L beginning 1 h before NA), reduced NA‐induced p38 MAPK activation and significantly accentuated NA‐induced cell death. In contrast, the mitogen‐activated protein kinase kinase ERK1/2 inhibitor PD98059 (at 1 µmol/L beginning 1 h before NA) did not significantly alter NA‐induced cell death. These effects of NA were mediated, in part, through α‐adrenoceptor because phenylephrine (100 µmol/L), like NA, also induced p38 MAPK activation. However, 100 µmol/L isoproterenol produced a sustained dephosphorylation of p38 MAPK. 4 These data show that NA‐induced p38 MAPK activation, through α‐adrenoceptor, has a protective role in cardiomyocytes to antagonize NA‐induced cell death. In contrast, β‐adrenoceptor stimulation produces dephosphorylation of p38 MAPK.