Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway

Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson’s disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR...

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Autores principales:	Peng Li, Li-Yan Yao, Yu-Jia Jiang, Dan-Dan Wang, Ting Wang, Yan-Ping Wu, Bai-Xiang Li, Xue-Ting Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Soybean isoflavones Atrazine Neurotoxicity Prevention Mitophagy Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/3550837a29e64bdc94913bfdc5038577
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spelling	oai:doaj.org-article:3550837a29e64bdc94913bfdc50385772021-11-06T04:14:46ZSoybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway0147-651310.1016/j.ecoenv.2021.112886https://doaj.org/article/3550837a29e64bdc94913bfdc50385772021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321009982https://doaj.org/toc/0147-6513Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson’s disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR neurotoxicity. Our previous studies demonstrated that ATR can impair mitochondrial function, leading to metabolic failure. Cells maintain mitochondrial quality through selective autophagic elimination, termed mitophagy. Soybean isoflavones (SI) possess multiple beneficial bioactivities, including preservation of mitochondria function, so it was hypothesized that SI can protect neurons against ATR toxicity by promoting mitophagy. Pretreatment of SH-SY5Y neurons with SI prevented ATR-induced metabolic failure and cytotoxicity as assessed by intracellular ATP, Na+-K+-ATPase activity, mitochondrial membrane potential, and cell viability assays. The neuroprotective efficacy of SI was superior to the major individual components genistein, daidzein, and glycitein. Ultrastructural analyses revealed that ATR induced mitochondrial damage, while SI promoted the sequestration of damaged mitochondria into autophagic vesicles. Soybean isoflavones also induced mitophagy as evidenced by upregulated expression of BNIP3/NIX, BEX2, and LC3-II, while co-treatment with the mitophagy inhibitor Mdivi-1 blocked SI-mediated neuroprotection and prevented SI from reversing ATR-induced BEX2 downregulation. Furthermore, BEX2 knockdown inhibited SI-induced activation of the BNIP3/NIX pathway, mitophagy, and neuroprotection. These findings suggest that SI protects against ATR-induced mitochondrial dysfunction and neurotoxicity by activating the BEX2/BNIP3/NIX pathway.Peng LiLi-Yan YaoYu-Jia JiangDan-Dan WangTing WangYan-Ping WuBai-Xiang LiXue-Ting LiElsevierarticleSoybean isoflavonesAtrazineNeurotoxicityPreventionMitophagyEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112886- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Soybean isoflavones Atrazine Neurotoxicity Prevention Mitophagy Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Soybean isoflavones Atrazine Neurotoxicity Prevention Mitophagy Environmental pollution TD172-193.5 Environmental sciences GE1-350 Peng Li Li-Yan Yao Yu-Jia Jiang Dan-Dan Wang Ting Wang Yan-Ping Wu Bai-Xiang Li Xue-Ting Li Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
description	Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson’s disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR neurotoxicity. Our previous studies demonstrated that ATR can impair mitochondrial function, leading to metabolic failure. Cells maintain mitochondrial quality through selective autophagic elimination, termed mitophagy. Soybean isoflavones (SI) possess multiple beneficial bioactivities, including preservation of mitochondria function, so it was hypothesized that SI can protect neurons against ATR toxicity by promoting mitophagy. Pretreatment of SH-SY5Y neurons with SI prevented ATR-induced metabolic failure and cytotoxicity as assessed by intracellular ATP, Na+-K+-ATPase activity, mitochondrial membrane potential, and cell viability assays. The neuroprotective efficacy of SI was superior to the major individual components genistein, daidzein, and glycitein. Ultrastructural analyses revealed that ATR induced mitochondrial damage, while SI promoted the sequestration of damaged mitochondria into autophagic vesicles. Soybean isoflavones also induced mitophagy as evidenced by upregulated expression of BNIP3/NIX, BEX2, and LC3-II, while co-treatment with the mitophagy inhibitor Mdivi-1 blocked SI-mediated neuroprotection and prevented SI from reversing ATR-induced BEX2 downregulation. Furthermore, BEX2 knockdown inhibited SI-induced activation of the BNIP3/NIX pathway, mitophagy, and neuroprotection. These findings suggest that SI protects against ATR-induced mitochondrial dysfunction and neurotoxicity by activating the BEX2/BNIP3/NIX pathway.
format	article
author	Peng Li Li-Yan Yao Yu-Jia Jiang Dan-Dan Wang Ting Wang Yan-Ping Wu Bai-Xiang Li Xue-Ting Li
author_facet	Peng Li Li-Yan Yao Yu-Jia Jiang Dan-Dan Wang Ting Wang Yan-Ping Wu Bai-Xiang Li Xue-Ting Li
author_sort	Peng Li
title	Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
title_short	Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
title_full	Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
title_fullStr	Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
title_full_unstemmed	Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway
title_sort	soybean isoflavones protect sh-sy5y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the bex2/bnip3/nix pathway
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3550837a29e64bdc94913bfdc5038577
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Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway

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