OBJECTIVE: To assess the effect of intravenous infusion of adrenergic, hypertrophic agonists on the activity of the ribosomal S6 (p70(S6)) kinase and the c-Jun NH(2)-terminal kinase 2 (JNK2) in adult rat hearts. ANIMALS AND METHODS: Noradrenaline (NA), isoproterenol (ISO), phenylephrine (PE), NA in combination with propranolol (NA+Prop) and NA in combination with prazosin (NA+Praz) were continuously intravenously infused in rat hearts for up to 72 h. The expression and phosphorylation status of JNK2 and p70(S6) kinase were investigated by western blotting and use of specific and phosphospecific antibodies. The activity of p70(S6) kinase was measured by incorporation of (32)P-labelled phosphate into the specific substrate S6 peptide. RESULTS: The ratio of left ventricular weight to body weight was increased by NA, and by alpha- (PE, NA+Prop) and beta-adrenergic (ISO, NA+Praz) stimulation. Right ventricular weight to body weight ratio was higher only after beta-adrenergic stimulation (ISO, NA+Praz). p70(S6) kinase activity was stimulated predominantly through beta-adrenoceptors in parallel with left and right ventricular hypertrophy. Activation of JNK2 was mainly dependent on alpha-adrenoceptor activation, which led to hypertrophy of only the left ventricle. CONCLUSIONS: The activation of p70(S6) kinase and JNK2 may be implicated in the development of catecholamine-induced cardiac hypertrophy in vivo.
OBJECTIVE: To assess the effect of intravenous infusion of adrenergic, hypertrophic agonists on the activity of the ribosomal S6 (p70(S6)) kinase and the c-Jun NH(2)-terminal kinase 2 (JNK2) in adult rat hearts. ANIMALS AND METHODS: Noradrenaline (NA), isoproterenol (ISO), phenylephrine (PE), NA in combination with propranolol (NA+Prop) and NA in combination with prazosin (NA+Praz) were continuously intravenously infused in rat hearts for up to 72 h. The expression and phosphorylation status of JNK2 and p70(S6) kinase were investigated by western blotting and use of specific and phosphospecific antibodies. The activity of p70(S6) kinase was measured by incorporation of (32)P-labelled phosphate into the specific substrate S6 peptide. RESULTS: The ratio of left ventricular weight to body weight was increased by NA, and by alpha- (PE, NA+Prop) and beta-adrenergic (ISO, NA+Praz) stimulation. Right ventricular weight to body weight ratio was higher only after beta-adrenergic stimulation (ISO, NA+Praz). p70(S6) kinase activity was stimulated predominantly through beta-adrenoceptors in parallel with left and right ventricular hypertrophy. Activation of JNK2 was mainly dependent on alpha-adrenoceptor activation, which led to hypertrophy of only the left ventricle. CONCLUSIONS: The activation of p70(S6) kinase and JNK2 may be implicated in the development of catecholamine-induced cardiac hypertrophy in vivo.
Authors: T Yamazaki; I Komuro; Y Zou; S Kudoh; T Mizuno; Y Hiroi; I Shiojima; H Takano; K i Kinugawa; O Kohmoto; T Takahashi; Y Yazaki Journal: J Mol Cell Cardiol Date: 1997-09 Impact factor: 5.000