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AuthorJaballah, Maiy
AuthorMohamed, Iman A.
AuthorAlemrayat, Bayan
AuthorAl-Sulaiti, Fatima
AuthorMlih, Mohamed
AuthorMraiche, Fatima
Available date2016-03-31T14:00:58Z
Publication Date2015-04
Publication NamePLoS ONE
ResourceScopus
CitationJaballah M, Mohamed IA, Alemrayat B, Al-Sulaiti F, Mlih M, Mraiche F (2015) Na+/H+ Exchanger Isoform 1 Induced Cardiomyocyte Hypertrophy Involves Activation of p90 Ribosomal S6 Kinase. PLoS ONE 10(4): e0122230.
ISSN1932-6203
URIhttp://dx.doi.org/10.1371/journal.pone.0122230
URIhttp://hdl.handle.net/10576/4299
AbstractStudies using pharmacological and genetic approaches have shown that increased activity/expression of the Na+/H+ exchanger isoform 1 (NHE1) play a critical role in the pathogenesis of cardiac hypertrophy. Despite the importance of NHE1 in cardiac hypertrophy, severe cerebrovascular side effects were associated with the use of NHE1 inhibitors when administered to patients with myocardial infarctions. p90 ribosomal S6 Kinase (RSK), a downstream regulator of the mitogen-activated protein kinase pathway, has also been implicated in cardiac hypertrophy. We hypothesized that RSK plays a role in the NHE1 induced cardiomyocyte hypertrophic response. Infection of H9c2 cardiomyoblasts with the active form of the NHE1 adenovirus induced hypertrophy and was associated with an increase in the phosphorylation of RSK (P<0.05). Parameters of hypertrophy such as cell area, protein content and atrial natriuretic mRNA expression were significantly reduced in H9c2 cardiomyoblasts infected with active NHE1 in the presence of dominant negative RSK (DN-RSK) (P<0.05). These results confirm that NHE1 lies upstream of RSK. Increased phosphorylation and activation of GATA4 at Ser261 was correlated with increased RSK phosphorylation. This increase was reversed upon inhibition of RSK or NHE1. These findings demonstrate for the first time that the NHE1 mediated hypertrophy is accounted for by increased activation and phosphorylation of RSK, which subsequently increased the phosphorylation of GATA4; eventually activating fetal gene transcriptional machinery.
SponsorQatar University Internal Grant (QUUG-CPH-CPH-11/12-1) and by the Undergraduate Research Experience Program (UREP11-027-3-005) provided by the Qatar National Research Fund, Doha, Qatar.
Languageen
PublisherPublic Library of Science
Subjectatrial natriuretic factor
messenger RNA
S6 kinase
sodium proton exchange protein 1
transcription factor GATA 4
adenovirus infection
animal cell
embryo
enzyme activation
enzyme phosphorylation
heart muscle cell
heart ventricle hypertrophy
pathogenesis
protein content
protein expression
protein function
protein protein interaction
Adenoviridae
TitleNa+/H+ exchanger isoform 1 induced cardiomyocyte hypertrophy involves activation of p90 ribosomal S6 Kinase
TypeArticle
Issue Number4
Volume Number10
dc.accessType Open Access


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