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The toxic effects and possible mechanisms of Brusatol on mouse oocytes

Brusatol is a natural quassinoid that shows a potential therapeutic use in cancer models by the inhibition of Nuclear factor erythroid 2-related factor 2 (Nrf2) and is capable of inducing a variety of biological effects. The effects of Brusatol on oocyte meiosis has not been addressed. In this study...

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Autores principales: Ma, Rujun, Li, Hongru, Zhang, Yu, Lin, Ying, Qiu, Xuhua, Xie, Min, Yao, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436816/
https://www.ncbi.nlm.nih.gov/pubmed/28542354
http://dx.doi.org/10.1371/journal.pone.0177844
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author Ma, Rujun
Li, Hongru
Zhang, Yu
Lin, Ying
Qiu, Xuhua
Xie, Min
Yao, Bing
author_facet Ma, Rujun
Li, Hongru
Zhang, Yu
Lin, Ying
Qiu, Xuhua
Xie, Min
Yao, Bing
author_sort Ma, Rujun
collection PubMed
description Brusatol is a natural quassinoid that shows a potential therapeutic use in cancer models by the inhibition of Nuclear factor erythroid 2-related factor 2 (Nrf2) and is capable of inducing a variety of biological effects. The effects of Brusatol on oocyte meiosis has not been addressed. In this study, we investigated the impact of Brusatol treatment on mouse oocyte maturation and its possible mechanism. Our data demonstrated that Brusatol treatment disrupted oocyte maturation and spindle/chromosome organization by modulating Nrf2-Cyclin B1 pathway, as the influence of Brusatol was compensated by the addition of Nrf2 activation plasmid, and the mRNA and protein levels of Cyclin B1 were severely reduced in oocytes following Nrf2 decline. In summary, our data support a model that Brusatol, through the inhibition of Nrf2, modulate Cyclin B1 levels, consequently disturbing proper spindle assembly and chromosome condensation in meiotic oocytes.
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spelling pubmed-54368162017-05-27 The toxic effects and possible mechanisms of Brusatol on mouse oocytes Ma, Rujun Li, Hongru Zhang, Yu Lin, Ying Qiu, Xuhua Xie, Min Yao, Bing PLoS One Research Article Brusatol is a natural quassinoid that shows a potential therapeutic use in cancer models by the inhibition of Nuclear factor erythroid 2-related factor 2 (Nrf2) and is capable of inducing a variety of biological effects. The effects of Brusatol on oocyte meiosis has not been addressed. In this study, we investigated the impact of Brusatol treatment on mouse oocyte maturation and its possible mechanism. Our data demonstrated that Brusatol treatment disrupted oocyte maturation and spindle/chromosome organization by modulating Nrf2-Cyclin B1 pathway, as the influence of Brusatol was compensated by the addition of Nrf2 activation plasmid, and the mRNA and protein levels of Cyclin B1 were severely reduced in oocytes following Nrf2 decline. In summary, our data support a model that Brusatol, through the inhibition of Nrf2, modulate Cyclin B1 levels, consequently disturbing proper spindle assembly and chromosome condensation in meiotic oocytes. Public Library of Science 2017-05-18 /pmc/articles/PMC5436816/ /pubmed/28542354 http://dx.doi.org/10.1371/journal.pone.0177844 Text en © 2017 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ma, Rujun
Li, Hongru
Zhang, Yu
Lin, Ying
Qiu, Xuhua
Xie, Min
Yao, Bing
The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title_full The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title_fullStr The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title_full_unstemmed The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title_short The toxic effects and possible mechanisms of Brusatol on mouse oocytes
title_sort toxic effects and possible mechanisms of brusatol on mouse oocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436816/
https://www.ncbi.nlm.nih.gov/pubmed/28542354
http://dx.doi.org/10.1371/journal.pone.0177844
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