Advanced search
1 file | 1.05 MB Add to list

Transcription factor FOXO3a is a negative regulator of cytotoxicity of Fusarium mycotoxin in GES-1 cells

(2018) TOXICOLOGICAL SCIENCES. 166(2). p.370-381
Author
Organization
Abstract
Molecular mechanism and key factors responsible for cytotoxicity against mycotoxin deoxynivalenol (DON) from Fusarium pathogens are rarely elucidated. In this study, rapid increases of ROS were first observed in human gastric epithelial (GES-1) cells under DON exposure. Mitochondrial DNA damage, impaired respiratory chain, and decreased oxygen consumption rate (OCR) values, as well as G2/M cell cycle arrest and apoptosis, were also detected. Via combinatorial approaches of a large-scale microarray of differentially expressed genes, high content and RNAi analysis, a transcription factor of Forkhead box O3 (FOXO3a) was found with crucial functionalities, regulated some apoptotic genes associated with mitochondrial toxicity and cell death after activation by nuclear translocation. Namely, knockdown of FOXO3a decreased the cytotoxicity of DON to GES-1 cells. Moreover, knockdown of the FOXO ortholog DAF16 in Caenorhabditis elegans increased the resistance to DON-induced cytotoxicity. Simultaneously, the signaling pathway of ROS/JNK/FOXO3a of DON-induced cytotoxicity was newly proposed. In total, FOXO3a via ROS/JNK/FOXO3a plays a critical role to function as negative regulator associating with DON-induced cytotoxicity, with the potential extending to other substances.
Keywords
MITOCHONDRIAL OXIDATIVE STRESS, GENE-EXPRESSION, APOPTOSIS, INHIBITION, TOXICITY, PATHWAYS, EXPOSURE, THERAPY, mitochondrial dysfunction, oxidative stress, FOXO3a nuclear, translocation, ROS/JNK/FOXO3a, DAF16

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.05 MB

Citation

Please use this url to cite or link to this publication:

MLA
Yang, Yunxia et al. “Transcription Factor FOXO3a Is a Negative Regulator of Cytotoxicity of Fusarium Mycotoxin in GES-1 Cells.” TOXICOLOGICAL SCIENCES 166.2 (2018): 370–381. Print.
APA
Yang, Yunxia, Yu, S., Liu, N., Xu, H., Gong, Y., Wu, Y., Wang, P., et al. (2018). Transcription factor FOXO3a is a negative regulator of cytotoxicity of Fusarium mycotoxin in GES-1 cells. TOXICOLOGICAL SCIENCES, 166(2), 370–381.
Chicago author-date
Yang, Yunxia, Song Yu, Na Liu, Haibin Xu, Yunyun Gong, Yongning Wu, Peilong Wang, et al. 2018. “Transcription Factor FOXO3a Is a Negative Regulator of Cytotoxicity of Fusarium Mycotoxin in GES-1 Cells.” Toxicological Sciences 166 (2): 370–381.
Chicago author-date (all authors)
Yang, Yunxia, Song Yu, Na Liu, Haibin Xu, Yunyun Gong, Yongning Wu, Peilong Wang, Xiaoou Su, Yucai Liao, Sarah De Saeger, Hans-Ulrich Humpf, and Aibo Wu. 2018. “Transcription Factor FOXO3a Is a Negative Regulator of Cytotoxicity of Fusarium Mycotoxin in GES-1 Cells.” Toxicological Sciences 166 (2): 370–381.
Vancouver
1.
Yang Y, Yu S, Liu N, Xu H, Gong Y, Wu Y, et al. Transcription factor FOXO3a is a negative regulator of cytotoxicity of Fusarium mycotoxin in GES-1 cells. TOXICOLOGICAL SCIENCES. 2018;166(2):370–81.
IEEE
[1]
Y. Yang et al., “Transcription factor FOXO3a is a negative regulator of cytotoxicity of Fusarium mycotoxin in GES-1 cells,” TOXICOLOGICAL SCIENCES, vol. 166, no. 2, pp. 370–381, 2018.
@article{8604447,
  abstract     = {Molecular mechanism and key factors responsible for cytotoxicity against mycotoxin deoxynivalenol (DON) from Fusarium pathogens are rarely elucidated. In this study, rapid increases of ROS were first observed in human gastric epithelial (GES-1) cells under DON exposure. Mitochondrial DNA damage, impaired respiratory chain, and decreased oxygen consumption rate (OCR) values, as well as G2/M cell cycle arrest and apoptosis, were also detected. Via combinatorial approaches of a large-scale microarray of differentially expressed genes, high content and RNAi analysis, a transcription factor of Forkhead box O3 (FOXO3a) was found with crucial functionalities, regulated some apoptotic genes associated with mitochondrial toxicity and cell death after activation by nuclear translocation. Namely, knockdown of FOXO3a decreased the cytotoxicity of DON to GES-1 cells. Moreover, knockdown of the FOXO ortholog DAF16 in Caenorhabditis elegans increased the resistance to DON-induced cytotoxicity. Simultaneously, the signaling pathway of ROS/JNK/FOXO3a of DON-induced cytotoxicity was newly proposed. In total, FOXO3a via ROS/JNK/FOXO3a plays a critical role to function as negative regulator associating with DON-induced cytotoxicity, with the potential extending to other substances.},
  author       = {Yang, Yunxia and Yu, Song and Liu, Na and Xu, Haibin and Gong, Yunyun and Wu, Yongning and Wang, Peilong and Su, Xiaoou and Liao, Yucai and De Saeger, Sarah and Humpf, Hans-Ulrich and Wu, Aibo},
  issn         = {1096-6080},
  journal      = {TOXICOLOGICAL SCIENCES},
  keywords     = {MITOCHONDRIAL OXIDATIVE STRESS,GENE-EXPRESSION,APOPTOSIS,INHIBITION,TOXICITY,PATHWAYS,EXPOSURE,THERAPY,mitochondrial dysfunction,oxidative stress,FOXO3a nuclear,translocation,ROS/JNK/FOXO3a,DAF16},
  language     = {eng},
  number       = {2},
  pages        = {370--381},
  title        = {Transcription factor FOXO3a is a negative regulator of cytotoxicity of Fusarium mycotoxin in GES-1 cells},
  url          = {http://dx.doi.org/10.1093/toxsci/kfy216},
  volume       = {166},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: