Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death

Cisplatin toxicity in renal tubular epithelial cells limits the therapeutic efficacy of this antineoplastic drug. In cultured human proximal tubular HK-2 cells (PTC) a prostaglandin uptake transporter (PGT)-dependent increase in intracellular prostaglandin E2 (iPGE2) mediates cisplatin's to...

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Authors: Yago Ibáñez, Julia, García Pastor, Coral|||0000-0002-7954-9172, Lucio Cazaña, Francisco Javier de|||0000-0001-9249-8501, Fernández Martínez, Ana Belén
Format: article
Publication Date:2020
Country:España
Institution:Universidad de Alcalá (UAH)
Repository:e_Buah Biblioteca Digital Universidad de Alcalá
Language:English
OAI Identifier:oai:ebuah.uah.es:10017/58972
Online Access:http://hdl.handle.net/10017/58972
https://dx.doi.org/10.1016/j.bbadis.2020.165795
Access Level:Open access
Keyword:4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid
Cisplatin
Human adenocarcinoma cells
Prostaglandin E2
Proximal tubular cells
Retinoic acid receptor-beta
Medicina
Medicine
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network_name_str España
repository_id_str
spelling Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell deathYago Ibáñez, JuliaGarcía Pastor, Coral|||0000-0002-7954-9172Lucio Cazaña, Francisco Javier de|||0000-0001-9249-8501Fernández Martínez, Ana Belén4,4′-Diisothiocyanostilbene-2,2′-disulfonic acidCisplatinHuman adenocarcinoma cellsProstaglandin E2Proximal tubular cellsRetinoic acid receptor-betaMedicinaMedicineCisplatin toxicity in renal tubular epithelial cells limits the therapeutic efficacy of this antineoplastic drug. In cultured human proximal tubular HK-2 cells (PTC) a prostaglandin uptake transporter (PGT)-dependent increase in intracellular prostaglandin E2 (iPGE2) mediates cisplatin's toxicity (i.e. increased cell death and loss of cell proliferation) so that it is prevented by PGT inhibitors. Here we found in cisplatin-treated PTC that 4,4?-diisothiocyanostilbene-2,2?-disulfonic acid (DIDS), a PGT inhibitor, prevented cisplatin's toxicity but not the increase in iPGE2. Because expression of retinoic acid receptor-? (RAR-?) is dependent on iPGE2 and because RAR-? is a regulator of cell survival and proliferation, we hypothesized that RAR-? might mediate the protective effect of DIDS against cisplatin's toxicity in PTC. Our results confirmed this hypothesis because: i) protection of PTC by DIDS was abolished by RAR-? antagonist LE-135; ii) DIDS increased the expression of RAR-? in PTC and prevented its decrease in cisplatin-treated PTC but not in cisplatin-treated human cervical adenocarcinoma HeLa cells in which DIDS failed to prevent cisplatin's toxicity; iii) while RAR-? expression decreased in cisplatin-treated PTC, RAR-? over-expression prevented cisplatin's toxicity. RAR-? agonist CH55 or RAR pan-agonist all-trans retinoic acid did not prevent cisplatin's toxicity, which suggests that RAR-? does not protect PTC through activation of gene transcription. In conclusion, RAR-? might be a new player in cisplatin-induced proximal tubular injury and the preservation of its expression in proximal tubules through treatment with DIDS might represent a novel strategy in the prevention of cisplatin nephrotoxicity without compromising cisplatin's chemotherapeutic effect on cancer cells.20202020-04-08journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/58972https://dx.doi.org/10.1016/j.bbadis.2020.165795reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/589722026-06-18T11:13:07Z
dc.title.none.fl_str_mv Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
title Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
spellingShingle Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
Yago Ibáñez, Julia
4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid
Cisplatin
Human adenocarcinoma cells
Prostaglandin E2
Proximal tubular cells
Retinoic acid receptor-beta
Medicina
Medicine
title_short Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
title_full Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
title_fullStr Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
title_full_unstemmed Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
title_sort Retinoic acid receptor-beta prevents cisplatin-induced proximal tubular cell death
dc.creator.none.fl_str_mv Yago Ibáñez, Julia
García Pastor, Coral|||0000-0002-7954-9172
Lucio Cazaña, Francisco Javier de|||0000-0001-9249-8501
Fernández Martínez, Ana Belén
author Yago Ibáñez, Julia
author_facet Yago Ibáñez, Julia
García Pastor, Coral|||0000-0002-7954-9172
Lucio Cazaña, Francisco Javier de|||0000-0001-9249-8501
Fernández Martínez, Ana Belén
author_role author
author2 García Pastor, Coral|||0000-0002-7954-9172
Lucio Cazaña, Francisco Javier de|||0000-0001-9249-8501
Fernández Martínez, Ana Belén
author2_role author
author
author
dc.subject.none.fl_str_mv 4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid
Cisplatin
Human adenocarcinoma cells
Prostaglandin E2
Proximal tubular cells
Retinoic acid receptor-beta
Medicina
Medicine
topic 4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid
Cisplatin
Human adenocarcinoma cells
Prostaglandin E2
Proximal tubular cells
Retinoic acid receptor-beta
Medicina
Medicine
description Cisplatin toxicity in renal tubular epithelial cells limits the therapeutic efficacy of this antineoplastic drug. In cultured human proximal tubular HK-2 cells (PTC) a prostaglandin uptake transporter (PGT)-dependent increase in intracellular prostaglandin E2 (iPGE2) mediates cisplatin's toxicity (i.e. increased cell death and loss of cell proliferation) so that it is prevented by PGT inhibitors. Here we found in cisplatin-treated PTC that 4,4?-diisothiocyanostilbene-2,2?-disulfonic acid (DIDS), a PGT inhibitor, prevented cisplatin's toxicity but not the increase in iPGE2. Because expression of retinoic acid receptor-? (RAR-?) is dependent on iPGE2 and because RAR-? is a regulator of cell survival and proliferation, we hypothesized that RAR-? might mediate the protective effect of DIDS against cisplatin's toxicity in PTC. Our results confirmed this hypothesis because: i) protection of PTC by DIDS was abolished by RAR-? antagonist LE-135; ii) DIDS increased the expression of RAR-? in PTC and prevented its decrease in cisplatin-treated PTC but not in cisplatin-treated human cervical adenocarcinoma HeLa cells in which DIDS failed to prevent cisplatin's toxicity; iii) while RAR-? expression decreased in cisplatin-treated PTC, RAR-? over-expression prevented cisplatin's toxicity. RAR-? agonist CH55 or RAR pan-agonist all-trans retinoic acid did not prevent cisplatin's toxicity, which suggests that RAR-? does not protect PTC through activation of gene transcription. In conclusion, RAR-? might be a new player in cisplatin-induced proximal tubular injury and the preservation of its expression in proximal tubules through treatment with DIDS might represent a novel strategy in the prevention of cisplatin nephrotoxicity without compromising cisplatin's chemotherapeutic effect on cancer cells.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-04-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/58972
https://dx.doi.org/10.1016/j.bbadis.2020.165795
url http://hdl.handle.net/10017/58972
https://dx.doi.org/10.1016/j.bbadis.2020.165795
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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