Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

Abstract Bisphenol A (BPA), a member of the environmental endocrine disruptors (EDCs), has recently received increased attention because of its effects on brain insulin resistance. Available data have indicated that brain insulin resistance may contribute to neurodegenerative diseases. However, the...

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Autores principales:	Tingwei Wang, Cuiwei Xie, Pengfei Yu, Fangfang Fang, Jingying Zhu, Jie Cheng, Aihua Gu, Jun Wang, Hang Xiao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a3b4e0a01b64e8d806e91946139fa06
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spelling	oai:doaj.org-article:6a3b4e0a01b64e8d806e91946139fa062021-12-02T12:32:24ZInvolvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity10.1038/s41598-017-07544-72045-2322https://doaj.org/article/6a3b4e0a01b64e8d806e91946139fa062017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07544-7https://doaj.org/toc/2045-2322Abstract Bisphenol A (BPA), a member of the environmental endocrine disruptors (EDCs), has recently received increased attention because of its effects on brain insulin resistance. Available data have indicated that brain insulin resistance may contribute to neurodegenerative diseases. However, the associated mechanisms that underlie BPA-induced brain-related outcomes remain largely unknown. In the present study, we identified significant insulin signaling disturbances in the SH-SY5Y cell line that were mediated by BPA, including the inhibition of physiological p-IR Tyr1355 tyrosine, p-IRS1 tyrosine 896, p-AKT serine 473 and p-GSK3α/β serine 21/9 phosphorylation, as well as the enhancement of IRS1 Ser307 phosphorylation; these effects were clearly attenuated by insulin and rosiglitazone. Intriguingly, Alzheimer’s disease (AD)-associated pathological proteins, such as BACE-1, APP, β-CTF, α-CTF, Aβ 1–42 and phosphorylated tau proteins (S199, S396, T205, S214 and S404), were substantially increased after BPA exposure, and these effects were abrogated by insulin and rosiglitazone treatment; these findings underscore the specific roles of insulin signaling in BPA-mediated AD-like neurotoxicity. Thus, an understanding of the regulation of insulin signaling may provide novel insights into potential therapeutic targets for BPA-mediated AD-like neurotoxicity.Tingwei WangCuiwei XiePengfei YuFangfang FangJingying ZhuJie ChengAihua GuJun WangHang XiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tingwei Wang Cuiwei Xie Pengfei Yu Fangfang Fang Jingying Zhu Jie Cheng Aihua Gu Jun Wang Hang Xiao Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
description	Abstract Bisphenol A (BPA), a member of the environmental endocrine disruptors (EDCs), has recently received increased attention because of its effects on brain insulin resistance. Available data have indicated that brain insulin resistance may contribute to neurodegenerative diseases. However, the associated mechanisms that underlie BPA-induced brain-related outcomes remain largely unknown. In the present study, we identified significant insulin signaling disturbances in the SH-SY5Y cell line that were mediated by BPA, including the inhibition of physiological p-IR Tyr1355 tyrosine, p-IRS1 tyrosine 896, p-AKT serine 473 and p-GSK3α/β serine 21/9 phosphorylation, as well as the enhancement of IRS1 Ser307 phosphorylation; these effects were clearly attenuated by insulin and rosiglitazone. Intriguingly, Alzheimer’s disease (AD)-associated pathological proteins, such as BACE-1, APP, β-CTF, α-CTF, Aβ 1–42 and phosphorylated tau proteins (S199, S396, T205, S214 and S404), were substantially increased after BPA exposure, and these effects were abrogated by insulin and rosiglitazone treatment; these findings underscore the specific roles of insulin signaling in BPA-mediated AD-like neurotoxicity. Thus, an understanding of the regulation of insulin signaling may provide novel insights into potential therapeutic targets for BPA-mediated AD-like neurotoxicity.
format	article
author	Tingwei Wang Cuiwei Xie Pengfei Yu Fangfang Fang Jingying Zhu Jie Cheng Aihua Gu Jun Wang Hang Xiao
author_facet	Tingwei Wang Cuiwei Xie Pengfei Yu Fangfang Fang Jingying Zhu Jie Cheng Aihua Gu Jun Wang Hang Xiao
author_sort	Tingwei Wang
title	Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
title_short	Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
title_full	Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
title_fullStr	Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
title_full_unstemmed	Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity
title_sort	involvement of insulin signaling disturbances in bisphenol a-induced alzheimer’s disease-like neurotoxicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6a3b4e0a01b64e8d806e91946139fa06
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Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

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