Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes

LRRC8 proteins have been shown to underlie the ubiquitous volume regulated anion channel (VRAC). VRAC channels are composed of the LRRC8A subunit and at least one among the LRRC8B-E subunits. In addition to their role in volume regulation, LRRC8 proteins have been implicated in the uptake of chemoth...

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Autores: Gradogna, Antonella, Gaitan Peñas, Hector|||0000-0001-9797-903X, Boccaccioa, Anna, Estévez, Raúl|||0000-0003-1579-650X
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:324858
Acceso en línea:https://ddd.uab.cat/record/324858
https://dx.doi.org/urn:doi:10.1080/19336950.2017.1284717
Access Level:acceso abierto
Palabra clave:Anion
Chloride channel
Cisplatin
Drug resistance
Oocyte
Volume regulation
VRAC
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spelling Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytesGradogna, AntonellaGaitan Peñas, Hector|||0000-0001-9797-903XBoccaccioa, AnnaEstévez, Raúl|||0000-0003-1579-650XAnionChloride channelCisplatinDrug resistanceOocyteVolume regulationVRACLRRC8 proteins have been shown to underlie the ubiquitous volume regulated anion channel (VRAC). VRAC channels are composed of the LRRC8A subunit and at least one among the LRRC8B-E subunits. In addition to their role in volume regulation, LRRC8 proteins have been implicated in the uptake of chemotherapeutic agents. We had found that LRRC8 channels can be conveniently expressed in Xenopus oocytes, a system without endogenous VRAC activity. The fusion with fluorescent proteins yielded constitutive activity for A/C, A/D and A/E heteromers. Here we tested the effect of the anticancer drug cisplatin on LRRC8A-VFP/8E-mCherry and LRRC8A-VFP/8D-mCherry co-expressing oocytes. Incubation with cisplatin dramatically activated currents for both subunit combinations, confirming that VRAC channels provide an uptake pathway for cisplatin and that intracellular cisplatin accumulation strongly activates the channels. Thus, specific activators of LRRC8 proteins might be useful tools to counteract chemotherapeutic drug resistance. 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/324858https://dx.doi.org/urn:doi:10.1080/19336950.2017.1284717reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-70377Generalitat de Catalunya https://doi.org/10.13039/501100002809 2014/SGR-01178open accesshttp://purl.org/coar/access_right/c_abf2Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.https://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3248582026-06-06T12:50:31Z
dc.title.none.fl_str_mv Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
title Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
spellingShingle Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
Gradogna, Antonella
Anion
Chloride channel
Cisplatin
Drug resistance
Oocyte
Volume regulation
VRAC
title_short Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
title_full Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
title_fullStr Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
title_full_unstemmed Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
title_sort Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
dc.creator.none.fl_str_mv Gradogna, Antonella
Gaitan Peñas, Hector|||0000-0001-9797-903X
Boccaccioa, Anna
Estévez, Raúl|||0000-0003-1579-650X
author Gradogna, Antonella
author_facet Gradogna, Antonella
Gaitan Peñas, Hector|||0000-0001-9797-903X
Boccaccioa, Anna
Estévez, Raúl|||0000-0003-1579-650X
author_role author
author2 Gaitan Peñas, Hector|||0000-0001-9797-903X
Boccaccioa, Anna
Estévez, Raúl|||0000-0003-1579-650X
author2_role author
author
author
dc.subject.none.fl_str_mv Anion
Chloride channel
Cisplatin
Drug resistance
Oocyte
Volume regulation
VRAC
topic Anion
Chloride channel
Cisplatin
Drug resistance
Oocyte
Volume regulation
VRAC
description LRRC8 proteins have been shown to underlie the ubiquitous volume regulated anion channel (VRAC). VRAC channels are composed of the LRRC8A subunit and at least one among the LRRC8B-E subunits. In addition to their role in volume regulation, LRRC8 proteins have been implicated in the uptake of chemotherapeutic agents. We had found that LRRC8 channels can be conveniently expressed in Xenopus oocytes, a system without endogenous VRAC activity. The fusion with fluorescent proteins yielded constitutive activity for A/C, A/D and A/E heteromers. Here we tested the effect of the anticancer drug cisplatin on LRRC8A-VFP/8E-mCherry and LRRC8A-VFP/8D-mCherry co-expressing oocytes. Incubation with cisplatin dramatically activated currents for both subunit combinations, confirming that VRAC channels provide an uptake pathway for cisplatin and that intracellular cisplatin accumulation strongly activates the channels. Thus, specific activators of LRRC8 proteins might be useful tools to counteract chemotherapeutic drug resistance.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/324858
https://dx.doi.org/urn:doi:10.1080/19336950.2017.1284717
url https://ddd.uab.cat/record/324858
https://dx.doi.org/urn:doi:10.1080/19336950.2017.1284717
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-70377
Generalitat de Catalunya https://doi.org/10.13039/501100002809 2014/SGR-01178
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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