1. Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells.
- Author
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Ribeiro-Silva L, Queiroz FO, da Silva AM, Hirata AE, and Arcisio-Miranda M
- Subjects
- Animals, Animals, Newborn, Biophysics, Brain cytology, Cell Line, Tumor, Cell Movement, Cells, Cultured, Chlorides pharmacology, Cytosol drug effects, Cytosol metabolism, Electric Stimulation, Flow Cytometry, Humans, Hydrogen-Ion Concentration, Membrane Potentials drug effects, Mice, Mice, Inbred C57BL, Neuroglia drug effects, Patch-Clamp Techniques, Zinc Compounds pharmacology, Glioblastoma metabolism, Ion Channels metabolism, Membrane Potentials physiology, Neuroglia physiology
- Abstract
Solid tumors tend to have a more glycolytic metabolism leading to an accumulation of acidic metabolites in their cytosol, and consequently, their intracellular pH (pHi) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (HV1) can regulate the pHi in several cancers. Here we report the functional expression of voltage gated proton channels in a human glioblastoma multiforme (GBM) cell line, the most common and lethal brain tumor. T98G cells presented an outward, slow activating voltage-dependent proton current, which was also ΔpH-dependent and inhibited by ZnCl2, characterizing it as being conducted by HV1 channels. Furthermore, blocking HV1 channels with ZnCl2 significantly reduced the pHi, cell survival, and migration, indicating an important role for HV1 for tumor proliferation and progression in GBM. Overall, our results suggest that HV1 channels can be a new therapeutic target for GBM.
- Published
- 2016
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