T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mito...

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Main Authors: Junhua Yang, Wenbo Guo, Jianhua Wang, Xianli Yang, Zhiqi Zhang, Zhihui Zhao
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/12/1/43
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author Junhua Yang
Wenbo Guo
Jianhua Wang
Xianli Yang
Zhiqi Zhang
Zhihui Zhao
author_facet Junhua Yang
Wenbo Guo
Jianhua Wang
Xianli Yang
Zhiqi Zhang
Zhihui Zhao
author_sort Junhua Yang
collection DOAJ
description T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.
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spelling doaj.art-caefef6f368549ea8e3621746df80d892022-12-22T02:22:12ZengMDPI AGToxins2072-66512020-01-011214310.3390/toxins12010043toxins12010043T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell LineJunhua Yang0Wenbo Guo1Jianhua Wang2Xianli Yang3Zhiqi Zhang4Zhihui Zhao5Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaInstitute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaInstitute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaInstitute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaInstitute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaInstitute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, ChinaT-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.https://www.mdpi.com/2072-6651/12/1/43t-2 toxinoxidative stressmitochondrial fusion/fissioncellular apoptosishl-7702 cells
spellingShingle Junhua Yang
Wenbo Guo
Jianhua Wang
Xianli Yang
Zhiqi Zhang
Zhihui Zhao
T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
Toxins
t-2 toxin
oxidative stress
mitochondrial fusion/fission
cellular apoptosis
hl-7702 cells
title T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
title_full T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
title_fullStr T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
title_full_unstemmed T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
title_short T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line
title_sort t 2 toxin induced oxidative stress leads to imbalance of mitochondrial fission and fusion to activate cellular apoptosis in the human liver 7702 cell line
topic t-2 toxin
oxidative stress
mitochondrial fusion/fission
cellular apoptosis
hl-7702 cells
url https://www.mdpi.com/2072-6651/12/1/43
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