ArticleFree radical biology & medicine2014
Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
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- Oxidative Stress in the Regulation of Autosis-Related Proteins.Antioxidants (Basel, Switzerland) · 2025Review
- Na,K-ATPase mediated and cardiotonic induced signaling in health and disease.Frontiers in physiology · 2025Review
- Interplay between the Redox System and Renal Tubular Transport.Antioxidants (Basel, Switzerland) · 2024Review
- The Na/K-ATPase α1/Src Signaling Axis Regulates Mitochondrial Metabolic Function and Redox Signaling in Human iPSC-Derived Cardiomyocytes.Biomedicines · 2023Article
- Article
- Involvement of NADPH oxidases in the Na/K‑ATPase/Src/ROS oxidant amplification loop in renal fibrosis.Molecular medicine reports · 2023Article
- Meta-data analysis of kidney stone disease highlights ATP1A1 involvement in renal crystal formation.Redox biology · 2023Article
- pNaKtide Inhibits Na/K-ATPase Signaling and Attenuates Obesity.Journal of clinical and medical sciences · 2023Article
- Regulation of Myogenesis by a Na/K-ATPase α1 Caveolin-Binding Motif.Stem cells (Dayton, Ohio) · 2022Article
- Role of adipocyte Na,K-ATPase oxidant amplification loop in cognitive decline and neurodegeneration.iScience · 2021Article
- Review
- The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart.The Journal of membrane biology · 2021Article
- NaMolecules (Basel, Switzerland) · 2021Review
- Attenuation of the Na/K‑ATPase/Src/ROS amplification signaling pathway by astaxanthin ameliorates myocardial cell oxidative stress injury.Molecular medicine reports · 2020Article
- Stress Signal Regulation by Na/K-ATPase As a New Approach to Promote Physiological Revascularization in a Mouse Model of Ischemic Retinopathy.Investigative ophthalmology & visual science · 2020Article
- Current Insights in Elucidation of Possible Molecular Mechanisms of the Juvenile Form of Batten Disease.International journal of molecular sciences · 2020Review
- Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy.Journal of the American Society of Nephrology : JASN · 2020Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
We have shown that Na/K-ATPase interacts with Src. Here, we test the role of this interaction in H2O2-induced activation of Src and ERK. We found that exposure of LLC-PK1 cells to H2O2 generated by the addition of glucose oxidase into the culture medium activated Src and ERK1/2. It also caused a modest reduction in the number of surface Na/K-ATPases and in ouabain-sensitive Rb(+) uptake. These effects of H2O2 seem similar to those induced by ouabain, a specific ligand of Na/K-ATPase, in LLC-PK1 cells. In accordance, we found that the effects of H2O2 on Src and ERK1/2 were inhibited in α1 Na/K-ATPase-knockdown PY-17 cells. Whereas expression of wild-type α1 or the A420P mutant α1 defective in Src regulation rescued the pumping activity in PY-17 cells, only α1, and not the A420P mutant, was able to restore the H2O2-induced activation of protein kinases. Consistent with this, disrupting the formation of the Na/K-ATPase/Src complex with pNaKtide attenuated the effects of H2O2 on the kinases. Moreover, a direct effect of H2O2 on Na/K-ATPase-mediated regulation of Src was demonstrated. Finally, H2O2 reduced the expression of E-cadherin through the Na/K-ATPase/Src-mediated signaling pathway. Taken together, the data suggest that the Na/K-ATPase/Src complex may serve as one of the receptor mechanisms for H2O2 to regulate Src/ERK protein kinases and consequently the phenotype of renal epithelial cells.
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