In rat neonatal ventricular myocytes, p38 activation mediated the development of myocyte hypertrophy and ANF expression, whereas JNK activation suppressed it.
In rat neonatal ventricular myocytes, p38 and JNK MAP kinases have opposing roles, with p38 mediating and JNK suppressing cardiomyocyte hypertrophy.
c-Jun N-terminal protein kinase (JNK) and p38, two distinct members of the mitogen-activated protein (MAP) kinase family, regulate gene expression in response to various extracellular stimuli, yet their physiological functions are not completely understood. In this report we show that JNK and p38 exerted opposing effects on the development of myocyte hypertrophy, which is an adaptive physiological process characterized by expression of embryonic genes and unique morphological changes. In rat neonatal ventricular myocytes, both JNK and p38 were stimulated by hypertrophic agonists like endothelin-1, phenylephrine, and leukemia inhibitory factor. Expression of MAP kinase kinase 6b (EE), a constitutive activator of p38, stimulated the expression of atrial natriuretic factor (ANF), which is a genetic marker of in vivo cardiac hypertrophy. Activation of p38 was required for ANF expression induced by the hypertrophic agonists. Furthermore, a specific p38 inhibitor, SB202190, significantly changed hypertrophic morphology induced by the agonists. Surprisingly, activation of JNK led to inhibition of ANF expression induced by MEK kinase 1 (MEKK1) and the hypertrophic agonists. MEKK1-induced ANF expression was also negatively regulated by expression of c-Jun. Our results demonstrate that p38 mediates, but JNK suppresses, the development of myocyte hypertrophy.
Nemoto et al. (1998) studied Cardiomyocyte Hypertrophy. p38 and JNK activation/inhibition vs. Untreated cells was evaluated on Atrial natriuretic factor (ANF) expression and hypertrophic morphology. In rat neonatal ventricular myocytes, p38 activation mediated the development of myocyte hypertrophy and ANF expression, whereas JNK activation suppressed it.