Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

Abstract The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was ac...

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Autores principales:	Gang Liu, Yan Yuan, Mengfei Long, Tongwang Luo, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Hui Zou, Ruilong Song, Yi Wang, Lin Wang, Zongping Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/195ac28e29514fe38459f4873d1f93c9
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spelling	oai:doaj.org-article:195ac28e29514fe38459f4873d1f93c92021-12-02T12:32:56ZBeclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture10.1038/s41598-017-00997-w2045-2322https://doaj.org/article/195ac28e29514fe38459f4873d1f93c92017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00997-whttps://doaj.org/toc/2045-2322Abstract The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis. The antiapoptotic effect of autophagy was blocked by 3-MA, an autophagy inhibitor. The interactions between Beclin-1 and Fas, FasL, FADD, caspase-8 and BID/tBID were relatively weak, with the exception of cleaved caspase-8, indicated that minimal interactions between these proteins and Beclin-1 are involved in maintaining the balance of autophagy and apoptosis. Beclin-1 precipitated with cleaved caspase-8 in a dose-dependent mannter, and the expression was increased by siRNA against Beclin-1. These data suggested that Beclin-1-mediated autophagy impairs the expression and function of cleaved caspase-8 to protect against Cd-induced activation of apopotosis through Fas/FasL signaling pathway.Gang LiuYan YuanMengfei LongTongwang LuoJianchun BianXuezhong LiuJianhong GuHui ZouRuilong SongYi WangLin WangZongping LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gang Liu Yan Yuan Mengfei Long Tongwang Luo Jianchun Bian Xuezhong Liu Jianhong Gu Hui Zou Ruilong Song Yi Wang Lin Wang Zongping Liu Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
description	Abstract The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis. The antiapoptotic effect of autophagy was blocked by 3-MA, an autophagy inhibitor. The interactions between Beclin-1 and Fas, FasL, FADD, caspase-8 and BID/tBID were relatively weak, with the exception of cleaved caspase-8, indicated that minimal interactions between these proteins and Beclin-1 are involved in maintaining the balance of autophagy and apoptosis. Beclin-1 precipitated with cleaved caspase-8 in a dose-dependent mannter, and the expression was increased by siRNA against Beclin-1. These data suggested that Beclin-1-mediated autophagy impairs the expression and function of cleaved caspase-8 to protect against Cd-induced activation of apopotosis through Fas/FasL signaling pathway.
format	article
author	Gang Liu Yan Yuan Mengfei Long Tongwang Luo Jianchun Bian Xuezhong Liu Jianhong Gu Hui Zou Ruilong Song Yi Wang Lin Wang Zongping Liu
author_facet	Gang Liu Yan Yuan Mengfei Long Tongwang Luo Jianchun Bian Xuezhong Liu Jianhong Gu Hui Zou Ruilong Song Yi Wang Lin Wang Zongping Liu
author_sort	Gang Liu
title	Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
title_short	Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
title_full	Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
title_fullStr	Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
title_full_unstemmed	Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture
title_sort	beclin-1-mediated autophagy protects against cadmium-activated apoptosis via the fas/fasl pathway in primary rat proximal tubular cell culture
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/195ac28e29514fe38459f4873d1f93c9
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Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture

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