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 delta. To date, the prominent isoform in heart has been thought to be p38alpha. 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. p38gamma and p38delta were expressed at protein levels comparable to p38alpha and 38beta, respectively. In the early phase of pressure-overload hypertrophy (1-7 days after constriction of the transverse aorta), the abundance of p38beta, p38gamma and p38delta mRNA increased; however, no corresponding changes were detected at the protein level. Confocal immunofluorescence studies revealed p38alpha and p38gamma 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), p38gamma immunoreactivity accumulated in the nucleus whereas the distribution of p38alpha remained unaffected. Hence, both p38alpha and p38gamma are prominent p38 isoforms in heart and p38gamma may play a role in mediating the changes in gene expression associated with cardiac remodeling during pressure-overload hypertrophy.
Dingar
Dharmendra
D
Montreal Heart Institute, 5000 Belanger St, Montréal, Québec, Canada.
Merlen
Clémence
C
Grandy
Scott
S
Gillis
Marc-Antoine
MA
Villeneuve
Louis R
LR
Mamarbachi
Aida M
AM
Fiset
Céline
C
Allen
Bruce G
BG
D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000201:enzymology*; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases