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المؤلفJaballah, Maiy
المؤلفMohamed, Iman A.
المؤلفAlemrayat, Bayan
المؤلفAl-Sulaiti, Fatima
المؤلفMlih, Mohamed
المؤلفMraiche, Fatima
تاريخ الإتاحة2016-03-31T14:00:58Z
تاريخ النشر2015-04
اسم المنشورPLoS ONE
الاقتباسJaballah 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.
الرقم المعياري الدولي للكتاب1932-6203
معرّف المصادر الموحدhttp://dx.doi.org/10.1371/journal.pone.0122230
معرّف المصادر الموحدhttp://hdl.handle.net/10576/4299
الملخصStudies 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.
راعي المشروعQatar 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.
اللغةen
الناشرPublic Library of Science
الموضوعatrial natriuretic factor
الموضوعmessenger RNA
الموضوعS6 kinase
الموضوعsodium proton exchange protein 1
الموضوعtranscription factor GATA 4
الموضوعadenovirus infection
الموضوعanimal cell
الموضوعembryo
الموضوعenzyme activation
الموضوعenzyme phosphorylation
الموضوعheart muscle cell
الموضوعheart ventricle hypertrophy
الموضوعpathogenesis
الموضوعprotein content
الموضوعprotein expression
الموضوعprotein function
الموضوعprotein protein interaction
الموضوعAdenoviridae
العنوانNa+/H+ exchanger isoform 1 induced cardiomyocyte hypertrophy involves activation of p90 ribosomal S6 Kinase
النوعArticle
رقم العدد4
رقم المجلد10


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