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AuthorMohamed, Iman A.
AuthorGadeau, Alain-Pierre
AuthorFliegel, Larry
AuthorLopaschuk, Gary
AuthorMlih, Mohamed
AuthorAbdulrahman, Nabeel
AuthorFillmore, Natasha
AuthorMraiche, Fatima
Available date2016-03-31T14:00:58Z
Publication Date2015-04
Publication NamePLoS ONE
CitationMohamed IA, Gadeau A-P, Fliegel L, Lopaschuk G, Mlih M, Abdulrahman N, et al. (2015) Na+/H+ Exchanger Isoform 1-Induced Osteopontin Expression Facilitates Cardiomyocyte Hypertrophy. PLoS ONE 10(4): e0123318.
ISSN1932-6203
URIhttp://dx.doi.org/10.1371/journal.pone.0123318
URIhttp://hdl.handle.net/10576/4297
AbstractEnhanced expression and activity of the Na+/H+ exchanger isoform 1 (NHE1) has been implicated in cardiomyocyte hypertrophy in various experimental models. The upregulation of NHE1 was correlated with an increase in osteopontin (OPN) expression in models of cardiac hypertrophy (CH), and the mechanism for this remains to be delineated. To determine whether the expression of active NHE1-induces OPN and contributes to the hypertrophic response in vitro, cardiomyocytes were infected with the active form of the NHE1 adenovirus or transfected with OPN silencing RNA (siRNA-OPN) and characterized for cardiomyocyte hypertrophy. Expression of NHE1 in cardiomyocytes resulted in a significant increase in cardiomyocyte hypertrophy markers: cell surface area, protein content, ANP mRNA and expression of phosphorylated-GATA4. NHE1 activity was also significantly increased in cardiomyocytes expressing active NHE1. Interestingly, transfection of cardiomyocytes with siRNA-OPN significantly abolished the NHE1-induced cardiomyocyte hypertrophy. siRNA-OPN also significantly reduced the activity of NHE1 in cardiomyocytes expressing NHE1 (68.5±0.24%; P<0.05), confirming the role of OPN in the NHE1-induced hypertrophic response. The hypertrophic response facilitated by NHE1-induced OPN occurred independent of the extracellular-signal-regulated kinases and Akt, but required p90-ribosomal S6 kinase (RSK). The ability of OPN to facilitate the NHE1-induced hypertrophic response identifies OPN as a potential therapeutic target to reverse the hypertrophic effect induced by the expression of active NHE1.
SponsorNational Priorities Research Program grant (NPRP 5-330-3-090) provided by the Qatar National Research Fund, Doha, Qatar.
Languageen
PublisherPublic Library of Science
Subjectatrial natriuretic factor
Subjectmessenger RNA
Subjectmitogen activated protein kinase 1
Subjectmitogen activated protein kinase 3
Subjectosteopontin
Subjectprotein kinase B
SubjectS6 kinase
Subjectsmall interfering RNA
Subjectsodium proton exchange protein 1
Subjecttranscription factor GATA 4
Subjectanimal cell
Subjectcell surface
Subjectcontrolled study
Subjectdown regulation
Subjectenzyme activity
Subjectgenetic transfection
Subjectheart hypertrophy
Subjectheart muscle cell
Subjectin vitro study
Subjectprotein content
Subjectprotein expression
Subjectprotein phosphorylation
Subjectrat
Subjectupregulation
SubjectAdenoviridae
TitleNa+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiomyocyte hypertrophy
TypeArticle
Issue Number4
Volume Number10


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