title: Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells.
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.
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , 04023-060 São Paulo, SP Brasil.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ribeiro-Silva
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , 04023-060 São Paulo, SP Brasil.
authors.forename: Fernanda Oliveira
authors.initials: FO
authors.lastname: Queiroz
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , 04023-060 São Paulo, SP Brasil.
authors.forename: Annielle Mendes Brito
authors.initials: AM
authors.lastname: da Silva
authors.affiliation: Departamento de Fisiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo , 04023-060 São Paulo, SP Brasil.
authors.forename: Aparecida Emiko
authors.initials: AE
authors.lastname: Hirata
authors.affiliation: Laboratório de Neurobiologia Estrutural e Funcional (LaNEF), Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo , 04023-060 São Paulo, SP Brasil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Arcisio-Miranda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001921:Brain / Q000166:cytology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D002712:Chlorides; D007473:Ion Channels; D017967:Zinc Compounds; C016837:zinc chloride
keywords: Proton channel; glioma; intracellular pH