Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells

Acrylamide (ACR) is a commonly used organic compound that exhibits evident neurotoxicity in humans. Our previous studies showed that the mechanisms of ACR-caused neurotoxicity included apoptosis, PERK-mediated endoplasmic reticulum stress, and autophagy, but the relationships among them were still u...

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Main Authors: Yiqi Wang, Ying Liu, Xing Zhang, Yang Jiao, Lian Duan, Ruijie Cheng, Ning Yang, Hong Yan
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/13/1/41
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author Yiqi Wang
Ying Liu
Xing Zhang
Yang Jiao
Lian Duan
Ruijie Cheng
Ning Yang
Hong Yan
author_facet Yiqi Wang
Ying Liu
Xing Zhang
Yang Jiao
Lian Duan
Ruijie Cheng
Ning Yang
Hong Yan
author_sort Yiqi Wang
collection DOAJ
description Acrylamide (ACR) is a commonly used organic compound that exhibits evident neurotoxicity in humans. Our previous studies showed that the mechanisms of ACR-caused neurotoxicity included apoptosis, PERK-mediated endoplasmic reticulum stress, and autophagy, but the relationships among them were still unclear. This paper investigated the relationships among apoptosis, autophagy, and the PERK pathway to demonstrate the mechanism of ACR neurotoxicity further. Different doses of ACR were set to value ACR toxicity. Then, a PERK inhibitor and autophagy inhibitor, GSK2606414 and 3-methyladenine (3-MA), were used separately to inhibit the PERK pathway and autophagy activation in SH-SY5Y cells under ACR treatment. With the increase of ACR dose, the apoptotic rate increased in a dose-dependent manner. After the inhibition of the PERK pathway, the activated apoptosis and autophagosome accumulation caused by ACR were alleviated. Under 3-MA and ACR treatment, the autophagy inhibition deteriorated apoptosis in SH-SY5Y cells but had no significant effect on ACR-induced PERK pathway activation; thus, PERK pathway-induced autophagy had an antiapoptotic role in this condition. This paper provides an experimental basis for exploring potential molecular targets to prevent and control ACR toxicity.
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institution Kabale University
issn 2305-6304
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Toxics
spelling doaj-art-fa744ada59db4ba6899c5849ebe5e86c2025-01-24T13:51:02ZengMDPI AGToxics2305-63042025-01-011314110.3390/toxics13010041Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y CellsYiqi Wang0Ying Liu1Xing Zhang2Yang Jiao3Lian Duan4Ruijie Cheng5Ning Yang6Hong Yan7MOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaDepartment of Laboratory Medicine, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310000, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaMOE Key Lab of Environment and Health, Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, ChinaAcrylamide (ACR) is a commonly used organic compound that exhibits evident neurotoxicity in humans. Our previous studies showed that the mechanisms of ACR-caused neurotoxicity included apoptosis, PERK-mediated endoplasmic reticulum stress, and autophagy, but the relationships among them were still unclear. This paper investigated the relationships among apoptosis, autophagy, and the PERK pathway to demonstrate the mechanism of ACR neurotoxicity further. Different doses of ACR were set to value ACR toxicity. Then, a PERK inhibitor and autophagy inhibitor, GSK2606414 and 3-methyladenine (3-MA), were used separately to inhibit the PERK pathway and autophagy activation in SH-SY5Y cells under ACR treatment. With the increase of ACR dose, the apoptotic rate increased in a dose-dependent manner. After the inhibition of the PERK pathway, the activated apoptosis and autophagosome accumulation caused by ACR were alleviated. Under 3-MA and ACR treatment, the autophagy inhibition deteriorated apoptosis in SH-SY5Y cells but had no significant effect on ACR-induced PERK pathway activation; thus, PERK pathway-induced autophagy had an antiapoptotic role in this condition. This paper provides an experimental basis for exploring potential molecular targets to prevent and control ACR toxicity.https://www.mdpi.com/2305-6304/13/1/41acrylamidePERK pathwayapoptosisautophagy
spellingShingle Yiqi Wang
Ying Liu
Xing Zhang
Yang Jiao
Lian Duan
Ruijie Cheng
Ning Yang
Hong Yan
Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
Toxics
acrylamide
PERK pathway
apoptosis
autophagy
title Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
title_full Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
title_fullStr Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
title_full_unstemmed Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
title_short Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells
title_sort acrylamide induces antiapoptotic autophagy and apoptosis by activating perk pathway in sh sy5y cells
topic acrylamide
PERK pathway
apoptosis
autophagy
url https://www.mdpi.com/2305-6304/13/1/41
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