The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis

Autores
Asuaje, Agustín; Smaldini, Paola Lorena; Martín, Pedro; Enrique, Nicolás Jorge; Orlowski, Alejandro; Aiello, Ernesto Alejandro; Gonzalez León, Carlos; Docena, Guillermo Horacio; Milesi, Verónica
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cellular energetic deregulation is widely known to produce an overproduction of acidic species in cancer cells. This acid overload must be counterbalanced with a high rate of H⁺ extrusion to maintain cell viability. In this sense, many H⁺ transporters have been reported to be crucial for cell survival and proposed as antineoplastic target. By the way, voltage-gated proton channels (Hv1) mediate highly selective H⁺ outward currents, capable to compensate acid burden in brief periods of time. This structure is canonically described acting as NADPH oxidase counterbalance in reactive oxygen species production. In this work, we show, for the first time in a oncohematologic cell line, that inhibition of Hv1 channels by Zn2⁺ and the more selective blocker 2-(6-chloro-1Hbenzimidazol-2-yl)guanidine (ClGBI) progressively decreases intracellular pH in resting conditions. This acidification is evident minutes after blockade and progresses under prolonged exposure (2, 17, and 48 h), and we firstly demonstrate that this is followed by cell death through apoptosis (annexin V binding). Altogether, these results contribute strong evidence that this channel might be a new therapeutic target in cancer.
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Exactas
Medicina
HVCN1
voltage-gated proton channel
intracellular pH
Apoptosis
leukemia
cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/109083
Acceder
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network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosisAsuaje, AgustínSmaldini, Paola LorenaMartín, PedroEnrique, Nicolás JorgeOrlowski, AlejandroAiello, Ernesto AlejandroGonzalez León, CarlosDocena, Guillermo HoracioMilesi, VerónicaCiencias ExactasMedicinaHVCN1voltage-gated proton channelintracellular pHApoptosisleukemiacancerCellular energetic deregulation is widely known to produce an overproduction of acidic species in cancer cells. This acid overload must be counterbalanced with a high rate of H⁺ extrusion to maintain cell viability. In this sense, many H⁺ transporters have been reported to be crucial for cell survival and proposed as antineoplastic target. By the way, voltage-gated proton channels (Hv1) mediate highly selective H⁺ outward currents, capable to compensate acid burden in brief periods of time. This structure is canonically described acting as NADPH oxidase counterbalance in reactive oxygen species production. In this work, we show, for the first time in a oncohematologic cell line, that inhibition of Hv1 channels by Zn2⁺ and the more selective blocker 2-(6-chloro-1Hbenzimidazol-2-yl)guanidine (ClGBI) progressively decreases intracellular pH in resting conditions. This acidification is evident minutes after blockade and progresses under prolonged exposure (2, 17, and 48 h), and we firstly demonstrate that this is followed by cell death through apoptosis (annexin V binding). Altogether, these results contribute strong evidence that this channel might be a new therapeutic target in cancer.Facultad de Ciencias ExactasInstituto de Estudios Inmunológicos y FisiopatológicosFacultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf251-261http://sedici.unlp.edu.ar/handle/10915/109083enginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00424-016-1928-0info:eu-repo/semantics/altIdentifier/issn/1432-2013info:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-016-1928-0info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:05:36Zoai:sedici.unlp.edu.ar:10915/109083Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:05:36.515SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
title The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
spellingShingle The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
Asuaje, Agustín
Ciencias Exactas
Medicina
HVCN1
voltage-gated proton channel
intracellular pH
Apoptosis
leukemia
cancer
title_short The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
title_full The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
title_fullStr The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
title_full_unstemmed The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
title_sort The inhibition of voltage-gated H⁺ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis
dc.creator.none.fl_str_mv Asuaje, Agustín
Smaldini, Paola Lorena
Martín, Pedro
Enrique, Nicolás Jorge
Orlowski, Alejandro
Aiello, Ernesto Alejandro
Gonzalez León, Carlos
Docena, Guillermo Horacio
Milesi, Verónica
author Asuaje, Agustín
author_facet Asuaje, Agustín
Smaldini, Paola Lorena
Martín, Pedro
Enrique, Nicolás Jorge
Orlowski, Alejandro
Aiello, Ernesto Alejandro
Gonzalez León, Carlos
Docena, Guillermo Horacio
Milesi, Verónica
author_role author
author2 Smaldini, Paola Lorena
Martín, Pedro
Enrique, Nicolás Jorge
Orlowski, Alejandro
Aiello, Ernesto Alejandro
Gonzalez León, Carlos
Docena, Guillermo Horacio
Milesi, Verónica
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Medicina
HVCN1
voltage-gated proton channel
intracellular pH
Apoptosis
leukemia
cancer
topic Ciencias Exactas
Medicina
HVCN1
voltage-gated proton channel
intracellular pH
Apoptosis
leukemia
cancer
dc.description.none.fl_txt_mv Cellular energetic deregulation is widely known to produce an overproduction of acidic species in cancer cells. This acid overload must be counterbalanced with a high rate of H⁺ extrusion to maintain cell viability. In this sense, many H⁺ transporters have been reported to be crucial for cell survival and proposed as antineoplastic target. By the way, voltage-gated proton channels (Hv1) mediate highly selective H⁺ outward currents, capable to compensate acid burden in brief periods of time. This structure is canonically described acting as NADPH oxidase counterbalance in reactive oxygen species production. In this work, we show, for the first time in a oncohematologic cell line, that inhibition of Hv1 channels by Zn2⁺ and the more selective blocker 2-(6-chloro-1Hbenzimidazol-2-yl)guanidine (ClGBI) progressively decreases intracellular pH in resting conditions. This acidification is evident minutes after blockade and progresses under prolonged exposure (2, 17, and 48 h), and we firstly demonstrate that this is followed by cell death through apoptosis (annexin V binding). Altogether, these results contribute strong evidence that this channel might be a new therapeutic target in cancer.
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description Cellular energetic deregulation is widely known to produce an overproduction of acidic species in cancer cells. This acid overload must be counterbalanced with a high rate of H⁺ extrusion to maintain cell viability. In this sense, many H⁺ transporters have been reported to be crucial for cell survival and proposed as antineoplastic target. By the way, voltage-gated proton channels (Hv1) mediate highly selective H⁺ outward currents, capable to compensate acid burden in brief periods of time. This structure is canonically described acting as NADPH oxidase counterbalance in reactive oxygen species production. In this work, we show, for the first time in a oncohematologic cell line, that inhibition of Hv1 channels by Zn2⁺ and the more selective blocker 2-(6-chloro-1Hbenzimidazol-2-yl)guanidine (ClGBI) progressively decreases intracellular pH in resting conditions. This acidification is evident minutes after blockade and progresses under prolonged exposure (2, 17, and 48 h), and we firstly demonstrate that this is followed by cell death through apoptosis (annexin V binding). Altogether, these results contribute strong evidence that this channel might be a new therapeutic target in cancer.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/109083
url http://sedici.unlp.edu.ar/handle/10915/109083
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00424-016-1928-0
info:eu-repo/semantics/altIdentifier/issn/1432-2013
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-016-1928-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
251-261
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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