Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells

T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis...

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Main Authors: Jing Wu, Yu Zhou, Zhihang Yuan, Jine Yi, Jingshu Chen, Naidong Wang, Yanan Tian
Format: Article
Language:English
Published: MDPI AG 2019-01-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/11/1/45
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author Jing Wu
Yu Zhou
Zhihang Yuan
Jine Yi
Jingshu Chen
Naidong Wang
Yanan Tian
author_facet Jing Wu
Yu Zhou
Zhihang Yuan
Jine Yi
Jingshu Chen
Naidong Wang
Yanan Tian
author_sort Jing Wu
collection DOAJ
description T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.
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spelling doaj.art-574d03994f7940e6a6eb620f9f7cf8c82022-12-22T02:53:29ZengMDPI AGToxins2072-66512019-01-011114510.3390/toxins11010045toxins11010045Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver CellsJing Wu0Yu Zhou1Zhihang Yuan2Jine Yi3Jingshu Chen4Naidong Wang5Yanan Tian6College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USACollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaT-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.http://www.mdpi.com/2072-6651/11/1/45T-2 toxintoxicityautophagyapoptosis
spellingShingle Jing Wu
Yu Zhou
Zhihang Yuan
Jine Yi
Jingshu Chen
Naidong Wang
Yanan Tian
Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
Toxins
T-2 toxin
toxicity
autophagy
apoptosis
title Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
title_full Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
title_fullStr Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
title_full_unstemmed Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
title_short Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
title_sort autophagy and apoptosis interact to modulate t 2 toxin induced toxicity in liver cells
topic T-2 toxin
toxicity
autophagy
apoptosis
url http://www.mdpi.com/2072-6651/11/1/45
work_keys_str_mv AT jingwu autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT yuzhou autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT zhihangyuan autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT jineyi autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT jingshuchen autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT naidongwang autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells
AT yanantian autophagyandapoptosisinteracttomodulatet2toxininducedtoxicityinlivercells