(Hypertension. 2001;37:1222.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Activation of Cardiac c-Jun NH2-Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load
From the Department of Medicine II, University of Mainz (T.A.F.), Mainz, Germany; the Institute of Clinical Biochemistry and Pathobiochemistry, University Medical Center (T.A.F., S.G.), Wurzburg, Germany; Institut für Medizinische Strahlenkunde und Zellforschung (S.L., E.F.), Wurzburg, Germany; and the Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School (K.S., P.F., M.A.P., R.A.K., J.M.P.), Boston, Mass.
Correspondence to Ralph A. Kelly, MD, Cardiology Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail rakelly{at}rics.bwh.harvard.edu
Abstract—The role of mitogen-activated protein kinase (MAPK) pathways as signal transduction intermediates of hemodynamic stress leading to cardiac hypertrophy in the adult heart is not fully established. In a rat model of pressure-overload hypertrophy, we examined whether activation of MAPK pathways, namely, the extracellular signal–regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), and the p38-MAPK pathways, occurs during rapid changes in hemodynamic load in vivo. A slight activation of ERK2 and marked increases in JNK1 and p38-MAPK activities were observed 30 minutes after aortic banding. The increase in p38-MAPK activity was accompanied by an increase in the phosphorylation of the p38 substrate MAPK–activated protein kinases 2 and 3. Activation of these kinases was coincident with an increase in phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and enhanced DNA binding of activator protein-1 factors. Thus, hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2.
Key Words: hypertrophy • protein kinases • transcription, genetic • hemodynamics
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