JNK1 is required to preserve cardiac function in the early response to pressure overload.
Cardiac stress consistently activates c-Jun NH(2)-terminal kinase (JNK) pathways, however the role of different members of the JNK family is unclear. In this study, we applied pressure overload (TAC) in mice with selective deletion of the three JNK genes (Jnk1(-/-), Jnk2(-/-), and Jnk3(-/-)). Following TAC, all three JNK knockout mouse lines developed cardiac hypertrophy similar to wild-type mice (WT), but only JNK1(-/-) mice displayed a significant reduction in fractional shortening after 3 and 7 days of pressure overload, associated with a significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and marked inflammatory infiltrate. After the acute deterioration stage, JNK1(-/-) mice underwent a slow recovery followed by a steady progression of cardiac dysfunction, becoming indistinguishable from WT after 12 weeks of TAC. These data suggest that JNK1 plays a protective role in response to pressure overload, preventing the early deterioration in cardiac function following an acute increase in afterload.
Department of Medicine, Cell Biology and Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Hideo
H
Tachibana
Cinzia
C
Perrino
Hideyuki
H
Takaoka
Roger J
RJ
Davis
Sathyamangla V
SV
Naga Prasad
Howard A
HA
Rockman
D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D001794:Blood Pressure; D006332:Cardiomegaly / Q000201:enzymology / Q000503:physiopathology*; D003251:Constriction, Pathologic; D005260:Female; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000235:genetics / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000502:physiology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D010641:Phenotype
D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8