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ACS Chem Neurosci ; 7(7): 864-9, 2016 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-27225904

RESUMEN

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.


Asunto(s)
Glioblastoma/metabolismo , Canales Iónicos/metabolismo , Potenciales de la Membrana/fisiología , Neuroglía/fisiología , Animales , Animales Recién Nacidos , Biofisica , Encéfalo/citología , Línea Celular Tumoral , Movimiento Celular , Células Cultivadas , Cloruros/farmacología , Citosol/efectos de los fármacos , Citosol/metabolismo , Estimulación Eléctrica , Citometría de Flujo , Humanos , Concentración de Iones de Hidrógeno , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Neuroglía/efectos de los fármacos , Técnicas de Placa-Clamp , Compuestos de Zinc/farmacología
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