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
.jpg)
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/109083
Ver los metadatos del registro completo
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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:UNLP2025-09-29T11:24:42Zoai: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:13292025-09-29 11:24:43.068SEDICI (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 |
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eng |
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