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Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels

PURPOSE: Unoprostone isopropyl (unoprostone) is a docosanoid currently used as an antiglaucoma agent. Unoprostone is known to have neuroprotective effects and to activate large conductance Ca(2+)-activated K(+) (BK) channels. Recently, unoprostone has been tested in clinical studies as a therapeutic...

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Autores principales: Tsuruma, Kazuhiro, Tanaka, Yuka, Shimazawa, Masamitsu, Mashima, Yukihiko, Hara, Hideaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250378/
https://www.ncbi.nlm.nih.gov/pubmed/22219651
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author Tsuruma, Kazuhiro
Tanaka, Yuka
Shimazawa, Masamitsu
Mashima, Yukihiko
Hara, Hideaki
author_facet Tsuruma, Kazuhiro
Tanaka, Yuka
Shimazawa, Masamitsu
Mashima, Yukihiko
Hara, Hideaki
author_sort Tsuruma, Kazuhiro
collection PubMed
description PURPOSE: Unoprostone isopropyl (unoprostone) is a docosanoid currently used as an antiglaucoma agent. Unoprostone is known to have neuroprotective effects and to activate large conductance Ca(2+)-activated K(+) (BK) channels. Recently, unoprostone has been tested in clinical studies as a therapeutic agent for retinitis pigmentosa (RP) and studies have demonstrated an improvement in retinal sensitivity and in the protection of central retinal sensitivity with its use. However, the mechanism of action underlying unoprostone’s protective effect in RP is not fully known. It is well known that the pathogenesis of RP can be accelerated by oxidative stress or light irradiation. Therefore, the current study investigated the effects and the underlying mechanism of action of unoprostone on oxidative stress- and light irradiation-induced damage in photoreceptor and retinal pigment epithelial cultures. METHODS: The study used the mouse retinal cone-cell line 661W to investigate the effects of unoprostone and its major metabolite, unoprostone-free acid (M1), on oxidative stress- or light irradiation-induced cell death, and a human retinal pigment epithelial cell line (ARPE-19), was used to investigate the effects on light-induced disruption of phagocytotic function in a latex bead assay. Additionally, we examined whether the effects of unoprostone and M1 were mediated by BK channels using iberiotoxin, a selective inhibitor of BK channels. RESULTS: Unoprostone and M1 protected against light- or H(2)O(2)-induced cell death in 661W cells, and against light-induced phagocytotic dysfunction in ARPE-19 cells. Additionally, iberiotoxin inhibited the protective effects of unoprostone and M1. CONCLUSIONS: These findings indicate that unoprostone has protective effects on oxidative stress- and light irradiation-induced damage in vitro and that these effects are mediated by activation of BK channels. This confirms that unoprostone represents a promising therapeutic agent for the treatment of RP and other retinal diseases.
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spelling pubmed-32503782012-01-04 Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels Tsuruma, Kazuhiro Tanaka, Yuka Shimazawa, Masamitsu Mashima, Yukihiko Hara, Hideaki Mol Vis Research Article PURPOSE: Unoprostone isopropyl (unoprostone) is a docosanoid currently used as an antiglaucoma agent. Unoprostone is known to have neuroprotective effects and to activate large conductance Ca(2+)-activated K(+) (BK) channels. Recently, unoprostone has been tested in clinical studies as a therapeutic agent for retinitis pigmentosa (RP) and studies have demonstrated an improvement in retinal sensitivity and in the protection of central retinal sensitivity with its use. However, the mechanism of action underlying unoprostone’s protective effect in RP is not fully known. It is well known that the pathogenesis of RP can be accelerated by oxidative stress or light irradiation. Therefore, the current study investigated the effects and the underlying mechanism of action of unoprostone on oxidative stress- and light irradiation-induced damage in photoreceptor and retinal pigment epithelial cultures. METHODS: The study used the mouse retinal cone-cell line 661W to investigate the effects of unoprostone and its major metabolite, unoprostone-free acid (M1), on oxidative stress- or light irradiation-induced cell death, and a human retinal pigment epithelial cell line (ARPE-19), was used to investigate the effects on light-induced disruption of phagocytotic function in a latex bead assay. Additionally, we examined whether the effects of unoprostone and M1 were mediated by BK channels using iberiotoxin, a selective inhibitor of BK channels. RESULTS: Unoprostone and M1 protected against light- or H(2)O(2)-induced cell death in 661W cells, and against light-induced phagocytotic dysfunction in ARPE-19 cells. Additionally, iberiotoxin inhibited the protective effects of unoprostone and M1. CONCLUSIONS: These findings indicate that unoprostone has protective effects on oxidative stress- and light irradiation-induced damage in vitro and that these effects are mediated by activation of BK channels. This confirms that unoprostone represents a promising therapeutic agent for the treatment of RP and other retinal diseases. Molecular Vision 2011-12-30 /pmc/articles/PMC3250378/ /pubmed/22219651 Text en Copyright © 2012 Molecular Vision. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tsuruma, Kazuhiro
Tanaka, Yuka
Shimazawa, Masamitsu
Mashima, Yukihiko
Hara, Hideaki
Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title_full Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title_fullStr Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title_full_unstemmed Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title_short Unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating BK channels
title_sort unoprostone reduces oxidative stress- and light-induced retinal cell death, and phagocytotic dysfunction, by activating bk channels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250378/
https://www.ncbi.nlm.nih.gov/pubmed/22219651
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