JCB logo
BD Biosciences
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 16 December 2002. doi:10.1083/jcb.200207149
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 419K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gupta, S.
Right arrow Articles by Sen, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gupta, S.
Right arrow Articles by Sen, S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2002/12/1019 $5.00
The Journal of Cell Biology, Volume 159, Number 6, 1019-1028

Article

 Activation of nuclear factor-{kappa}B is necessary for myotrophin-induced cardiac hypertrophy

Sudhiranjan Gupta1, Nicole H. Purcell2, Anning Lin2 and Subha Sen1

1 Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195
2 Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637

Address correspondence to Subha Sen, Department of Molecular Cardiology (NB 50), The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Tel.: (216) 444-2056. Fax: (216) 444-3110. E-mail: sens{at}ccf.org

The transcription factor nuclear factor-{kappa}B (NF-{kappa}B) regulates expression of a variety of genes involved in immune responses, inflammation, proliferation, and programmed cell death (apoptosis). Here, we show that in rat neonatal ventricular cardiomyocytes, activation of NF-{kappa}B is involved in the hypertrophic response induced by myotrophin, a hypertrophic activator identified from spontaneously hypertensive rat heart and cardiomyopathic human hearts. Myotrophin treatment stimulated NF-{kappa}B nuclear translocation and transcriptional activity, accompanied by I{kappa}B-{alpha} phosphorylation and degradation. Consistently, myotrophin-induced NF-{kappa}B activation was enhanced by wild-type I{kappa}B kinase (IKK) ß and abolished by the dominant-negative IKKß or a general PKC inhibitor, calphostin C. Importantly, myotrophin-induced expression of two hypertrophic genes (atrial natriuretic factor [ANF] and c-myc) and also enhanced protein synthesis were partially inhibited by a potent NF-{kappa}B inhibitor, pyrrolidine dithio-carbamate (PDTC), and calphostin C. Expression of the dominant-negative form of I{kappa}B-{alpha} or IKKß also partially inhibited the transcriptional activity of ANF induced by myotrophin. These findings suggest that the PKC–IKK–NF-{kappa}B pathway may play a critical role in mediating the myotrophin-induced hypertrophic response in cardiomyocytes.

Key Words: myotrophin; NF-{kappa}B; PKC; cardiac hypertrophy; signal transduction


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents