Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

p38 mitogen-activated protein kinases (MAPKs) are serine/threonine specific protein kinases that respond to cellular stress and regulate a broad range of cellular activities. There are four major isoforms of p38 MAPK: alpha, beta, gamma, and gamma. To date, the prominent isoform in heart has been thought to be p38 alpha. We examined the expression of each p38 isoform at both the mRNA and protein level in murine heart. mRNA for all four p38 isoforms was detected. p38 gamma and p38 delta were expressed at protein levels comparable to p38 alpha and 38 beta, respectively. In the early phase of pressure-overload hypertrophy (1-7 days after constriction of the transverse aorta), the abundance of p38 beta, p38 gamma and p38 delta mRNA increased; however, no corresponding changes were detected at the protein level. Confocal immunofluorescence studies revealed p38 alpha and p38 gamma in both the cytoplasm and nucleus. In the established phase of hypertrophy induced by chronic pressure overload (7-28 days after constriction of the transverse aorta), p38 gamma immunoreactivity accumulated in the nucleus whereas the distribution of p38 alpha remained unaffected. Hence, both p38 alpha and p38 gamma are prominent p38 isoforrns in heart and p38 gamma may play a role in mediating the changes in gene expression associated with cardiac remodeling during pressure-overload hypertrophy. (C) 2010 Elsevier Inc. All rights reserved.