JNK1 is required to preserve cardiac function in the early response to pressure overload.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tachibana, H; Perrino, C; Takaoka, H; Davis, RJ; Naga Prasad, SV; Rockman, HA

Published Date

  • May 19, 2006

Published In

Volume / Issue

  • 343 / 4

Start / End Page

  • 1060 - 1066

PubMed ID

  • 16579967

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2006.03.065

Language

  • eng

Conference Location

  • United States