Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart Hiroyuki Nakayama * , Benjamin J. Wilkin * , Ilona Bodi † and Jeffery D. Molkentin * ,1 * Department of Pediatrics, University of Cincinnati, Children’s Hospital Medical Center, Cincinnati, Ohio, USA; and † Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA 1 Correspondence: Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA. E-mail: jeff.molkentin@cchmc.org The manner in which Ca 2+ -sensitive signaling proteins are activated in contracting cardiomyocytes is an intriguing theoretical problem given that the cytoplasm is continually bathed with systolic Ca 2+ concentrations that should maximally activate most Ca 2+ -sensitive signaling kinases and phosphatases. Store-operated Ca 2+ entry, partially attributed to transient receptor potential (TRP) proteins, can mediate activation of the Ca 2+ -sensitive phosphatase calcineurin in nonexcitable cells. Here we investigated the gain-of-function phenotype associated with TRPC3 expression in the mouse heart using transgenesis to examine the potential role of store-operated Ca 2+ entry in regulating cardiac calcineurin activation and ensuing hypertrophy/myopathy. Adult myocytes isolated from TRPC3 transgenic mice showed abundant store-operated Ca 2+ entry that was inhibited with SKF96365 but not verapamil or KB-R7943. Associated with this induction in store-operated Ca 2+ entry, TRPC3 transgenic mice showed increased calcineurin-nuclear factor of activated T cells (NFAT) activation in vivo , cardiomyopathy, and increased hypertrophy after neuroendocrine agonist or pressure overload stimulation. The cardiomyopathic phenotype and increased hypertrophy after pressure overload stimulation were blocked by targeted disruption of the calcineurin A ß gene. Thus, enhanced store-operated Ca 2+ entry in the heart can regulate calcineurin-NFAT signaling in vivo , which could secondarily impact the hypertrophic response and cardiomyopathy.—Nakayama, H., Wilkin, B. J., Bodi, I., Molkentin, J. D. Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart. Key Words: signaling • calcium • store-operated • NFAT
End of preview. The entire article is 11 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/calcineurin-dependent-cardiomyopathy-is-activated-by-trpc-in-the-adult-f0vbHHZQUk
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart
Nakayama, Hiroyuki; Wilkin, Benjamin J.; Bodi, Ilona; Molkentin, Jeffery D.
Follow The FASEB Journal
, Volume 20 (10): 1660
Fed of American Socs for Experimental Biology – Aug 1, 2006
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
