CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
research
Inhibition of AP-1 signaling by JDP2 overexpression protects cardiomyocytes against hypertrophy and apoptosis induction
Authors
Alona Würfel
Ami Aronheim
+24 more
Aronheim
Bettina Meyering
Christian Hill
Frantz
Gerhild Euler
Heger
Hilal-Dandan
Jacqueline Heger
Jeong
Kehat
Klaus-Dieter Schlüter
Langer
Martin Weber
Nadruz
Omura
Peter Ferdinandy
Pfaffl
Pinson
Rainer Schulz
Sabri
Schneiders
Schäfer
Taimor
Takemoto
Publication date
23 December 2014
Publisher
'Oxford University Press (OUP)'
Doi
Cite
Abstract
AimsExpression and activity of the transcription factor AP-1 are enhanced during cardiac remodelling and heart failure progression. In order to test if AP-1 inhibition may limit processes contributing to cardiac remodelling, ventricular cardiomyocytes of mice with cardiac overexpression of the AP-1 inhibitor JDP2 were analysed under stimulation of hypertrophy, apoptosis, or contractile function.Methods and resultsThree models of JDP2 overexpressing mice were analysed: JDP2 was overexpressed either life-long, for 7 weeks, or 1 week. Then cardiomyocytes were isolated and stimulated with β-adrenoceptor agonist isoprenaline (ISO, 50 nM). This enhanced cross-sectional area and the rate of protein synthesis in WT but not in JDP2 overexpressing cardiomyocytes. To induce apoptosis, cardiomyocytes were stimulated with 3 ng/mL TGFβ1. Again, JDP2 overexpression prevented apoptosis induction compared with WT cells. Determination of contractile function under electrical stimulation at 2 Hz revealed enhancement of cell shortening, and contraction and relaxation velocities under increasing ISO concentrations (0.3-30 nM) in WT cells. This inotropic effect was abrogated in JDP2 overexpression cells. Responsiveness to increased extracellular calcium concentrations was also impaired in JDP2 overexpressing cardiomyocytes. Simultaneously, a reduction of SERCA expression was found in JDP2 mice.ConclusionA central role of AP-1 in the induction of hypertrophy and apoptosis in cardiomyocytes is demonstrated. Besides these protective effects of AP-1 inhibition on factors of cardiac remodelling, AP-1-inhibition impairs contractile function. Therefore, AP-1 acts as a double-edged sword that mediates mal-adaptive cardiac remodelling, but is required for maintaining a proper contractile function of cardiomyocytes. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
Semmelweis Repository
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:repo.lib.semmelweis.hu:123...
Last time updated on 11/11/2016
Crossref
See this paper in CORE
Go to the repository landing page
Download from data provider
info:doi/10.1093%2Fcvr%2Fcvt09...
Last time updated on 04/12/2019