ArticlePloS one2015
Na+/H+ exchanger isoform 1 induced cardiomyocyte hypertrophy involves activation of p90 ribosomal s6 kinase.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Protective Effect of the NHE1 Inhibitor Buthutin A on Oxidative Stress-Induced Apoptosis in HUVECs.ACS omega · 2026Article
- Novel role of GRK2 in isoprenaline-induced activation of NaMolecular biology reports · 2025Article
- Design, synthesis and biological evaluation of buthutin derivatives as cardioprotective agents.Natural products and bioprospecting · 2025Article
- Imatinib‑ and ponatinib‑mediated cardiotoxicity in zebrafish embryos and H9c2 cardiomyoblasts.Molecular medicine reports · 2024Article
- The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.Journal of cardiovascular translational research · 2024Review
- Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.Current drug targets · 2023Article
- The Remaining Conundrum of the Role of the NaReviews in cardiovascular medicine · 2022Review
- Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression.Molecular and cellular biochemistry · 2022Article
- Comment on "Smooth or Risky Revisit of an Old Malaria Drug for COVID-19?"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- Structural and Functional Changes in the NaInternational journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies 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.
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