Various intracellular or intercellular stimuli have been associated with the development of cardiac cell hypertrophy. However, the mechanisms underlying this association are not completely understood. In a previous study we determined that ZAK mRNA expression is abundant in heart. ZAK is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the stress-activated protein kinase/c-jun N-terminal kinase pathway and activates NF-κB. We, therefore, investigated the potential involvement of ZAK (which in cultured H9c2 cardiomyoblast cell is a positive mediator of cell hypertrophy). Our results showed that the expression of a wild-type form of ZAK induces the characteristic hypertrophic growth features, including increased cell size, elevated atrial natriuretic factor expression, and increased actin fiber organization.
