Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway

Cadmium (Cd) chloride, a ubiquitous environmental pollutant, impairs nerve function and is associated with neurodegeneration. The aim of this study was to investigate the molecular mechanism of nerve damage caused by Cd exposure in swine. Six-week-old weaned pigs were exposed to CdCl2 (20 mg/kg) for...

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Autores principales:	Yue Zhu, Peixian Luan, Xiao Liu, Jun Bao, Qi Liu, Jingzeng Cai, Jie Yang, Ziwei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cadmium Autophagy Apoptosis Neurodegeneration Swine Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/182c87a1701d4db0a97b1b05bcf71996
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spelling	oai:doaj.org-article:182c87a1701d4db0a97b1b05bcf719962021-12-04T04:32:06ZCrosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway0147-651310.1016/j.ecoenv.2021.113053https://doaj.org/article/182c87a1701d4db0a97b1b05bcf719962021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011659https://doaj.org/toc/0147-6513Cadmium (Cd) chloride, a ubiquitous environmental pollutant, impairs nerve function and is associated with neurodegeneration. The aim of this study was to investigate the molecular mechanism of nerve damage caused by Cd exposure in swine. Six-week-old weaned pigs were exposed to CdCl2 (20 mg/kg) for 40 days. Subsequently, real-time quantitative PCR (qRT–PCR) and western blotting (WB) were applied to validate the genes. Our results showed that Cd exposure downregulated protein expression of p-PI3K/PI3K, p-AKT/AKT, and mTOR in the cerebral cortex and cerebellum, whereas protein expression of AMPK, Beclin-1, LC3-II/LC3-I, ATG5 and ATG7 was upregulated. Moreover, we found that Cd exposure stimulated increased mRNA and protein levels of Caspase-3, Caspase-9, and Bax and decreased Bcl-2 levels to initiate apoptosis. In addition, our results revealed that Cd exposure destroyed the nerve cell structure in the cerebral cortex and reduced the number of nerve cells in the cerebellum. The severity of cerebellar injuries was higher than that in the cerebral cortex. Overall, we found that Cd led to PI3K/AKT inhibition and AMPK activation to enhance autophagy and induce apoptosis. Our research paves a pathway for mining neurodegeneration in response to Cd exposure.Yue ZhuPeixian LuanXiao LiuJun BaoQi LiuJingzeng CaiJie YangZiwei ZhangElsevierarticleCadmiumAutophagyApoptosisNeurodegenerationSwineEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 113053- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cadmium Autophagy Apoptosis Neurodegeneration Swine Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Cadmium Autophagy Apoptosis Neurodegeneration Swine Environmental pollution TD172-193.5 Environmental sciences GE1-350 Yue Zhu Peixian Luan Xiao Liu Jun Bao Qi Liu Jingzeng Cai Jie Yang Ziwei Zhang Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
description	Cadmium (Cd) chloride, a ubiquitous environmental pollutant, impairs nerve function and is associated with neurodegeneration. The aim of this study was to investigate the molecular mechanism of nerve damage caused by Cd exposure in swine. Six-week-old weaned pigs were exposed to CdCl2 (20 mg/kg) for 40 days. Subsequently, real-time quantitative PCR (qRT–PCR) and western blotting (WB) were applied to validate the genes. Our results showed that Cd exposure downregulated protein expression of p-PI3K/PI3K, p-AKT/AKT, and mTOR in the cerebral cortex and cerebellum, whereas protein expression of AMPK, Beclin-1, LC3-II/LC3-I, ATG5 and ATG7 was upregulated. Moreover, we found that Cd exposure stimulated increased mRNA and protein levels of Caspase-3, Caspase-9, and Bax and decreased Bcl-2 levels to initiate apoptosis. In addition, our results revealed that Cd exposure destroyed the nerve cell structure in the cerebral cortex and reduced the number of nerve cells in the cerebellum. The severity of cerebellar injuries was higher than that in the cerebral cortex. Overall, we found that Cd led to PI3K/AKT inhibition and AMPK activation to enhance autophagy and induce apoptosis. Our research paves a pathway for mining neurodegeneration in response to Cd exposure.
format	article
author	Yue Zhu Peixian Luan Xiao Liu Jun Bao Qi Liu Jingzeng Cai Jie Yang Ziwei Zhang
author_facet	Yue Zhu Peixian Luan Xiao Liu Jun Bao Qi Liu Jingzeng Cai Jie Yang Ziwei Zhang
author_sort	Yue Zhu
title	Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
title_short	Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
title_full	Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
title_fullStr	Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
title_full_unstemmed	Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway
title_sort	crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the pi3k/akt/ampk pathway
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/182c87a1701d4db0a97b1b05bcf71996
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Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/AKT/AMPK pathway

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