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TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic miceThe transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.
Document ID
20040141573
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Zhang, D.
(Baylor College of Medicine Houston, Texas 77030, United States)
Gaussin, V.
Taffet, G. E.
Belaguli, N. S.
Yamada, M.
Schwartz, R. J.
Michael, L. H.
Overbeek, P. A.
Schneider, M. D.
Date Acquired
August 22, 2013
Publication Date
May 1, 2000
Publication Information
Publication: Nature medicine
Volume: 6
Issue: 5
ISSN: 1078-8956
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cardiopulmonary
NASA Program Biomedical Research and Countermeasures
Non-NASA Center

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