Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells

Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells

Author Ribeiro-Silva, Luisa Autor UNIFESP Google Scholar
Queiroz, Fernanda Oliveira Autor UNIFESP Google Scholar
Brito da Silva, Annielle Mendes Autor UNIFESP Google Scholar
Hirata, Aparecida Emiko Autor UNIFESP Google Scholar
Arcisio-Miranda, Manoel Autor UNIFESP Google Scholar
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 (pH(i)) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (H(v)1) can regulate the pH(i) 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 Delta pH-dependent and inhibited by ZnCl2, characterizing it as being conducted by H(v)1 channels. Furthermore, blocking H(v)1 channels with ZnCl2 significantly reduced the pH(i), cell survival, and migration, indicating an important role for H(v)1 for tumor proliferation and progression in GBM. Overall, our results suggest that H(v)1 channels can be a new therapeutic target for GBM.
Keywords Proton channel
intracellular pH
xmlui.dri2xhtml.METS-1.0.item-coverage Washington
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Processo Fapesp)
Fapesp fellowship
Capes fellowship
Grant number FAPESP: 2010/52077-9
FAPESP: 2011/52099-5
FAPESP: 2013/26005-9
Date 2016
Published in Acs Chemical Neuroscience. Washington, v. 7, n. 7, p. 864-869, 2016.
ISSN 1948-7193 (Sherpa/Romeo, impact factor)
Publisher Amer Chemical Soc
Extent 864-869
Origin http://dx.doi.org/10.1021/acschemneuro.6b00083
Access rights Closed access
Type Article
Web of Science ID WOS:000380297500004
URI https://repositorio.unifesp.br/handle/11600/57656

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