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

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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Asuaje, Agustín, Martín, Pedro, Enrique, Nicolás Jorge, Diaz Zegarra, Leandro Agustín, Smaldini, Paola Lorena, Docena, Guillermo Horacio, Milesi, Verónica
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107777
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5972794&blobtype=pdf
https://www.tandfonline.com/doi/full/10.1080/19336950.2017.1331799
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107777
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
spellingShingle Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
Asuaje, Agustín
Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
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
topic_facet Ciencias Exactas
Ciencias Médicas
antihistaminic
Apoptosis
cancer
diphenhydramine
HVCN1
intracellular pH
leukemia
proton channels
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.
format Articulo
Articulo
author Asuaje, Agustín
Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
author_facet Asuaje, Agustín
Martín, Pedro
Enrique, Nicolás Jorge
Diaz Zegarra, Leandro Agustín
Smaldini, Paola Lorena
Docena, Guillermo Horacio
Milesi, Verónica
author_sort Asuaje, Agustín
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
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
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/107777
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5972794&blobtype=pdf
https://www.tandfonline.com/doi/full/10.1080/19336950.2017.1331799
work_keys_str_mv AT asuajeagustin diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT martinpedro diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT enriquenicolasjorge diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT diazzegarraleandroagustin diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT smaldinipaolalorena diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT docenaguillermohoracio diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
AT milesiveronica diphenhydramineinhibitsvoltagegatedprotonchannelshv1andinducesacidificationinleukemicjurkattcellsnewinsightsintotheproapoptoticeffectsofantihistaminicdrugs
bdutipo_str Repositorios
_version_ 1764820443609432068

Ejemplares similares