Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NOi Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway
Joint Authors
Chu, Miensheng
Kim, Taehoon
Koshman, Yevgeniya
Samarel, Allen M.
Iyengar, Rekha
Russell, Brenda
Source
Journal of Signal Transduction
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-07-26
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Intracellular nitric oxide (NOi) is a physiological regulator of excitation-contraction coupling, but is also involved in the development of cardiac dysfunction during hypertrophy and heart failure.
To determine whether contractile activity regulates nitric oxide synthase (NOS) expression, spontaneously contracting, neonatal rat ventricular myocytes (NRVM) were treat with L-type calcium channel blockers (nifedipine and verapamil) or myosin II ATPase inhibitors (butanedione monoxime (BDM) and blebbistatin) to produce contractile arrest.
Both types of inhibitors significantly reduced iNOS but not eNOS expression, and also reduced NOi production.
Inhibiting contractile activity also reduced focal adhesion kinase (FAK) and AKT phosphorylation.
Contraction-induced iNOS expression required FAK and phosphatidylinositol 3-kinase (PI(3)K), as both PF573228 and LY294002 (10 μM, 24 h) eliminated contraction-induced iNOS expression.
Similarly, shRNAs specific for FAK (shFAK) caused FAK knockdown, reduced AKT phosphorylation at T308 and S473, and reduced iNOS expression.
In contrast, shRNA-mediated knockdown of PYK2, the other member of the FAK-family of protein tyrosine kinases, had much less of an effect.
Conversely, overexpression of a constitutively active form of FAK (CD2-FAK) or AKT (Myr-AKT) reversed the inhibitory effect of BDM on iNOS expression and NOi production.
Thus, contraction-induced iNOS expression and NOi production in NRVM are mediated via a FAK-PI(3)K-AKT signaling pathway.
American Psychological Association (APA)
Chu, Miensheng& Koshman, Yevgeniya& Iyengar, Rekha& Kim, Taehoon& Russell, Brenda& Samarel, Allen M.. 2012. Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NOi Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway. Journal of Signal Transduction،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-474317
Modern Language Association (MLA)
Chu, Miensheng…[et al.]. Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NOi Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway. Journal of Signal Transduction No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-474317
American Medical Association (AMA)
Chu, Miensheng& Koshman, Yevgeniya& Iyengar, Rekha& Kim, Taehoon& Russell, Brenda& Samarel, Allen M.. Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NOi Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway. Journal of Signal Transduction. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-474317
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-474317