Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic dru...

Autores
Asuaje, Agustín; Martín, Pedro; Enrique, Nicolás Jorge; Diaz Zegarra, Leandro Agustín; Smaldini, Paola Lorena; Docena, Guillermo Horacio; Milesi, Verónica
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos
Materia
Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/107777
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/107777
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugsAsuaje, AgustínMartín, PedroEnrique, Nicolás JorgeDiaz Zegarra, Leandro AgustínSmaldini, Paola LorenaDocena, Guillermo HoracioMilesi, VerónicaCiencias ExactasCiencias MédicasantihistaminicApoptosiscancerdiphenhydramineHVCN1intracellular pHleukemiaproton channelsAn established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.Facultad de Ciencias ExactasInstituto de Estudios Inmunológicos y Fisiopatológicos2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf58-64http://sedici.unlp.edu.ar/handle/10915/107777enginfo:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5972794&blobtype=pdfinfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/19336950.2017.1331799info:eu-repo/semantics/altIdentifier/issn/1933-6969info:eu-repo/semantics/altIdentifier/pmid/28514187info:eu-repo/semantics/altIdentifier/doi/10.1080/19336950.2017.1331799info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:04:47Zoai:sedici.unlp.edu.ar:10915/107777Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:04:47.287SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
title Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
spellingShingle Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
Asuaje, Agustín
Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
title_short Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
title_full Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
title_fullStr Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
title_full_unstemmed Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
title_sort Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs
dc.creator.none.fl_str_mv Asuaje, Agustín
Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
author Asuaje, Agustín
author_facet Asuaje, Agustín
Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
author_role author
author2 Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
topic Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
dc.description.none.fl_txt_mv An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos
description An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/10915/107777
url http://sedici.unlp.edu.ar/handle/10915/107777
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5972794&blobtype=pdf
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/19336950.2017.1331799
info:eu-repo/semantics/altIdentifier/issn/1933-6969
info:eu-repo/semantics/altIdentifier/pmid/28514187
info:eu-repo/semantics/altIdentifier/doi/10.1080/19336950.2017.1331799
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
58-64
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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