ArticlePflugers Archiv : European journal of physiology2009
alpha-ENaC is a functional element of the hypertonicity-induced cation channel in HepG2 cells and it mediates proliferation.
Article in Pflugers Archiv : European journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
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- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Cancer Salt Nostalgia.Cells · 2021Article
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Differential expression of epithelial sodium channels in human RCC associated with the prognosis and tumor stage: Evidence from integrate analysis.Journal of Cancer · 2020Article
- Sodium homeostasis in the tumour microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Potassium and Sodium Channels and the Warburg Effect: Biophysical Regulation of Cancer Metabolism.Bioelectricity · 2019Article
- Titanium dioxide nanoparticles induce mitochondria-associated apoptosis in HepG2 cells.RSC advances · 2018Article
- Hypertonicity-induced cation channels in HepG2 cells: architecture and role in proliferation vs. apoptosis.The Journal of physiology · 2018Article
- Cell Volume Control in Healthy Brain and Neuropathologies.Current topics in membranes · 2018Review
- MRP4 regulates ENaC-dependent CREB/COX-2/PGEOncotarget · 2017Article
- Inflammatory role of high salt level in tumor microenvironment (Review).International journal of oncology · 2017Review
- Over-expression of ASIC1a promotes proliferation via activation of the β-catenin/LEF-TCF axis and is associated with disease outcome in liver cancer.Oncotarget · 2017Article
- Extraoral Taste Receptor Discovery: New Light on Ayurvedic Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2017Review
- Aldosterone alters the chromatin structure of the murine endothelin-1 gene.Life sciences · 2016Article
- Channelling frozen cells to survival after thawing: opening the door to cryo-physiology.The Journal of physiology · 2016Article
- Adaptive responses of cell hydration to a low temperature arrest.The Journal of physiology · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular correlate of hypertonicity-induced cation channels (HICCs) and their role in proliferation vs. apoptosis is a matter of debate. We report in this paper that, in whole-cell patch-clamp recordings, hypertonic stress (340-->450 mosM) reversibly increased the Na(+) conductance of HepG2 cells from 0.8 to 5.8 nS. The effect was dose-dependently inhibited by flufenamate and amiloride, known blockers of HICCs, with some 50% efficiency at 300 muM. In parallel, both drugs decreased HepG2 cell proliferation [in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and with automatic cell counting]. Small interfering RNA (siRNA) silencing of the alpha-subunit of the epithelial Na(+) channel (ENaC) reduced hypertonicity-induced Na(+) currents to 60%, whereas the rate of HepG2 cell proliferation was approximately half of that of the control. Moreover, alpha-ENaC siRNA inhibited the regulatory volume increase of HepG2 cells (measured with scanning acoustic microscopy) by 60%. In florescence-activated cell sorting measurements, silencing of alpha-ENaC led to a significant decrease in the G1 and an increase in the G2/M phase of the cell cycle, whereas the S phase was not changing. Finally (determined by a caspase 3/7 assay), HICC inhibition by flufenamate and silencing of alpha-ENaC increased the rate of apoptosis in HepG2 cells. It is concluded that alpha-ENaC is one functional element of the HICC in HepG2 cells and that the channel is an important mediator of cell proliferation; likewise, HICC blockage shifts the system from a proliferative into a rather apoptotic one. This is the first report of a role of alpha-ENaC in cell proliferation.
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