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| Status |
Public on Jan 10, 2012 |
| Title |
PKCz-mediated Gaq stimulation of the ERK5 pathway is involved in cardiac hypertrophy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Methodology/Principal Findings: We have explored the mechanisms involved in Gq-coupled GPCR-mediated stimulation of the ERK5 pathway and its functional consequences in cardiac hypertrophy using both cultured cardiac cells and an animal model of angiotensin- dependent induction of cardiac hypertrophy in wild-type and PKCz knockout mice. We find that PKCζ is required for the activation of the ERK5 pathway by Gq-coupled GPCR in cardiomyocytes and in cardiac fibroblasts. Stimulation of ERK5 by angiotensin II is blocked upon pharmacological inhibition or siRNA-mediated silencing of PKCz in primary cultures of cardiac cells and in cardiomyocytes isolated from PKCz-deficient mice. Moreover, these mice do not develop cardiac hypertrophy upon chronic challenge with angiotensin II, as assessed by morphological, biomarker, electrocardiographic and global gene expression pattern analysis.
Conclusion/Significance: Our data put forward that PKCζ is essential for Gq- dependent ERK5 activation in cardiac cells and indicate a key cardiac physiological role for this recently described Gaq/PKCz/MEK5 signaling axis.
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| Overall design |
Littermate wild-type and PKCz -/- male mice (32 weeks of age) were subjected to continuous infusion of angiotensin II (or PBS as a control) for 14 days, a well established model for the induction of cardiac hypertrohy
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| Contributor(s) |
García-Hoz C, Sánchez-Fernández G, García-Escudero R, Fernandez-Velasco M, Palacios-Garcia J, Ruiz-Meana M, Diaz-Meco MT, Leitges M, Moscat J, Garcia-Dorado D, Bosca L, Mayor F Jr, Ribas C |
| Citation(s) |
22232556 |
| |
| Submission date |
May 09, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Ramon Garcia-Escudero |
| E-mail(s) |
ramon.garcia@ciemat.es, rgescudero@gmail.com
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| Organization name |
CIEMAT
|
| Department |
Biomedical Innovation
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| Lab |
Molecular and Traslational Oncology
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| Street address |
Avda Complutense 40, Ed 70A
|
| City |
Madrid |
| State/province |
Madrid |
| ZIP/Postal code |
28040 |
| Country |
Spain |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA140351 |
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