Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes
Gradogna, Antonella (National Research Council)
Gaitan Peñas, Hector (Universitat de Barcelona)
Boccaccioa, Anna (National Research Council)
Estévez, Raúl (Universitat de Barcelona)

Fecha:	2017
Resumen:	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.
Ayudas:	Ministerio de Economía y Competitividad SAF2015-70377 Generalitat de Catalunya 2014/SGR-01178
Derechos:	Aquest 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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Materia:	Anion ; Chloride channel ; Cisplatin ; Drug resistance ; Oocyte ; Volume regulation ; VRAC
Publicado en:	Channels (Austin, Tex.), Vol. 11, Num. 3 (May 2017) , p. 254-260, ISSN 1933-6969

DOI: 10.1080/19336950.2017.1284717
PMID: 28121479

Postprint 9 p, 383.1 KB

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