Activation of cardiac c-Jun NH(2)-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load.
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 NH(2)-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.
Fischer
T A
TA
Department of Medicine II, University of Mainz, Mainz, Germany.
Ludwig
S
S
Flory
E
E
Gambaryan
S
S
Singh
K
K
Finn
P
P
Pfeffer
M A
MA
Kelly
R A
RA
Pfeffer
J M
JM
D051698:Activating Transcription Factor 2; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000201:enzymology* / Q000503:physiopathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases