T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway

The mechanisms by which T-2 toxin induces senescence in neurons, along with the involvement of hypoxia-inducible factor-1α (HIF-1α), remain poorly understood. Using human neuroblastoma SH-SY5Y cells as a model, T-2 toxin (6 nM, 1–48 h) induced senescence in SH-SY5Y cells, leading to cell cycle arres...

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Main Authors: Yating Wang, Xu Wang, Qinghua Wu
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/S0147651324015409
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author Yating Wang
Xu Wang
Qinghua Wu
author_facet Yating Wang
Xu Wang
Qinghua Wu
author_sort Yating Wang
collection DOAJ
description The mechanisms by which T-2 toxin induces senescence in neurons, along with the involvement of hypoxia-inducible factor-1α (HIF-1α), remain poorly understood. Using human neuroblastoma SH-SY5Y cells as a model, T-2 toxin (6 nM, 1–48 h) induced senescence in SH-SY5Y cells, leading to cell cycle arrest. This was mediated by the upregulation of proteins involved in cell cycle regulation and stimulation of IL-6 and NF-κB expression. T-2 toxin rapidly triggered the expression of senescence-associated β-galactosidase, disrupted mitochondrial function, and altered the levels of Alzheimer’s disease-associated proteins (Tau, p-Tau, and APP). T-2 toxin also transiently elevated HIF-1α levels. Notably, HIF-1α regulated the expression of cell cycle inhibitory proteins (p16, p21, p53) and senescence-associated secretory phenotype factors (IL-8, IL-6, CCL2), along with the expression of senescence-associated β-galactosidase, thereby exacerbating T-2 toxin-induced cellular senescence. These findings underscore the vital role of HIF-1α in T-2 toxin-induced senescence in SH-SY5Y cells.
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spelling doaj-art-3e0eae3892704a52ba327de039f814842025-01-23T05:25:39ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117464T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathwayYating Wang0Xu Wang1Qinghua Wu2College of Life Science, Yangtze University, Jingzhou 434025, ChinaNational Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University (HZAU), Wuhan 430070, ChinaCollege of Life Science, Yangtze University, Jingzhou 434025, China; Corresponding author.The mechanisms by which T-2 toxin induces senescence in neurons, along with the involvement of hypoxia-inducible factor-1α (HIF-1α), remain poorly understood. Using human neuroblastoma SH-SY5Y cells as a model, T-2 toxin (6 nM, 1–48 h) induced senescence in SH-SY5Y cells, leading to cell cycle arrest. This was mediated by the upregulation of proteins involved in cell cycle regulation and stimulation of IL-6 and NF-κB expression. T-2 toxin rapidly triggered the expression of senescence-associated β-galactosidase, disrupted mitochondrial function, and altered the levels of Alzheimer’s disease-associated proteins (Tau, p-Tau, and APP). T-2 toxin also transiently elevated HIF-1α levels. Notably, HIF-1α regulated the expression of cell cycle inhibitory proteins (p16, p21, p53) and senescence-associated secretory phenotype factors (IL-8, IL-6, CCL2), along with the expression of senescence-associated β-galactosidase, thereby exacerbating T-2 toxin-induced cellular senescence. These findings underscore the vital role of HIF-1α in T-2 toxin-induced senescence in SH-SY5Y cells.http://www.sciencedirect.com/science/article/pii/S0147651324015409T-2 toxin, cellular senescence, HIF-1α, Alzheimer’s disease, SH-SY5Yp53
spellingShingle Yating Wang
Xu Wang
Qinghua Wu
T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
Ecotoxicology and Environmental Safety
T-2 toxin, cellular senescence, HIF-1α, Alzheimer’s disease, SH-SY5Y
p53
title T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
title_full T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
title_fullStr T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
title_full_unstemmed T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
title_short T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1α/p53/p21 pathway
title_sort t 2 toxin induces senescence in human neuroblastoma sh sy5y cells by regulating the hif 1α p53 p21 pathway
topic T-2 toxin, cellular senescence, HIF-1α, Alzheimer’s disease, SH-SY5Y
p53
url http://www.sciencedirect.com/science/article/pii/S0147651324015409
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AT xuwang t2toxininducessenescenceinhumanneuroblastomashsy5ycellsbyregulatingthehif1ap53p21pathway
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