GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells

Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress...

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Main Authors: Jiahui Meng, Linlin Xu, Bingchun Ma, Chaoju Hao, Yanning Guo, Jinglei Wang, Jiaxiang Chen
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324015021
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author Jiahui Meng
Linlin Xu
Bingchun Ma
Chaoju Hao
Yanning Guo
Jinglei Wang
Jiaxiang Chen
author_facet Jiahui Meng
Linlin Xu
Bingchun Ma
Chaoju Hao
Yanning Guo
Jinglei Wang
Jiaxiang Chen
author_sort Jiahui Meng
collection DOAJ
description Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function. Furthermore, we demonstrate that transcription factors cAMP response element-binding protein 1 (CREB1) and POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) synergistically enhance Gabarapl1 gene transcription by interacting with its promoter region, contributing to ACR-induced autophagy in mouse Leydig cells. Notably, our findings suggest a reciprocal regulation between PATZ1 and CREB1. This study suggests the critical role of GABARAPL1 in ACR-induced autophagy of mouse Leydig cells, shedding light on the underlying mechanism of ACR-caused male reproductive impairment.
format Article
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institution Kabale University
issn 0147-6513
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Ecotoxicology and Environmental Safety
spelling doaj-art-63fe62e6b67d4193b1717b9a7abe56fb2025-01-23T05:25:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117426GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cellsJiahui Meng0Linlin Xu1Bingchun Ma2Chaoju Hao3Yanning Guo4Jinglei Wang5Jiaxiang Chen6Department of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaDepartment of Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaLibrary, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China; Correspondence to: Department of Physiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, 461 Bayi Road, Donghu District, Nanchang 330006, PR China.Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function. Furthermore, we demonstrate that transcription factors cAMP response element-binding protein 1 (CREB1) and POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) synergistically enhance Gabarapl1 gene transcription by interacting with its promoter region, contributing to ACR-induced autophagy in mouse Leydig cells. Notably, our findings suggest a reciprocal regulation between PATZ1 and CREB1. This study suggests the critical role of GABARAPL1 in ACR-induced autophagy of mouse Leydig cells, shedding light on the underlying mechanism of ACR-caused male reproductive impairment.http://www.sciencedirect.com/science/article/pii/S0147651324015021AcrylamideLeydig cellsAutophagyGABARAPL1
spellingShingle Jiahui Meng
Linlin Xu
Bingchun Ma
Chaoju Hao
Yanning Guo
Jinglei Wang
Jiaxiang Chen
GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
Ecotoxicology and Environmental Safety
Acrylamide
Leydig cells
Autophagy
GABARAPL1
title GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
title_full GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
title_fullStr GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
title_full_unstemmed GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
title_short GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells
title_sort gabarapl1 is essential for acr induced autophagic cell death of mouse leydig cells
topic Acrylamide
Leydig cells
Autophagy
GABARAPL1
url http://www.sciencedirect.com/science/article/pii/S0147651324015021
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