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Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells

Food contaminants of bacterial or fungal origin frequently contaminate staple foods to various extents. Among others, the bacterial toxin cereulide (CER) and the mycotoxin deoxynivalenol (DON) co-occur in a mixed diet and are absorbed by the human body. Both toxins exert dis-tinctive mitotoxic poten...

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Autores principales: Beisl, Julia, Pahlke, Gudrun, Ehling-Schulz, Monika, Del Favero, Giorgia, Marko, Doris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880806/
https://www.ncbi.nlm.nih.gov/pubmed/35202179
http://dx.doi.org/10.3390/toxins14020151
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author Beisl, Julia
Pahlke, Gudrun
Ehling-Schulz, Monika
Del Favero, Giorgia
Marko, Doris
author_facet Beisl, Julia
Pahlke, Gudrun
Ehling-Schulz, Monika
Del Favero, Giorgia
Marko, Doris
author_sort Beisl, Julia
collection PubMed
description Food contaminants of bacterial or fungal origin frequently contaminate staple foods to various extents. Among others, the bacterial toxin cereulide (CER) and the mycotoxin deoxynivalenol (DON) co-occur in a mixed diet and are absorbed by the human body. Both toxins exert dis-tinctive mitotoxic potential. As damaged mitochondria are removed via autophagy, mitochondrial and lysosomal toxicity were assessed by applying low doses of single and combined toxins (CER 0.1–50 ng/mL; DON 0.01–5 µg/mL) to HepG2 liver cells. In addition to cytotoxicity assays, RT-qPCR was performed to investigate genes involved in lysosomal biogenesis and autophagy. CER and DON caused significant cytotoxicity on HepG2 cells after 5 and 24 h over a broad concentration range. CER, alone and in combination with DON, increased the transcription of the autophagy related genes coding for the microtubule associated protein 1A/1B light chain 3 (LC3) and sequestome 1 (SQSTM1) as well as LC3 protein expression which was determined using immunocytochemistry. DON increased LC3 protein expression without induction of gene transcription, hence it seems plausible that CER and DON act on different pathways. The results support the hypothesis that CER induces autophagy via the LC3 pathway and damaged mitochondria are therefore eliminated.
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spelling pubmed-88808062022-02-26 Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells Beisl, Julia Pahlke, Gudrun Ehling-Schulz, Monika Del Favero, Giorgia Marko, Doris Toxins (Basel) Article Food contaminants of bacterial or fungal origin frequently contaminate staple foods to various extents. Among others, the bacterial toxin cereulide (CER) and the mycotoxin deoxynivalenol (DON) co-occur in a mixed diet and are absorbed by the human body. Both toxins exert dis-tinctive mitotoxic potential. As damaged mitochondria are removed via autophagy, mitochondrial and lysosomal toxicity were assessed by applying low doses of single and combined toxins (CER 0.1–50 ng/mL; DON 0.01–5 µg/mL) to HepG2 liver cells. In addition to cytotoxicity assays, RT-qPCR was performed to investigate genes involved in lysosomal biogenesis and autophagy. CER and DON caused significant cytotoxicity on HepG2 cells after 5 and 24 h over a broad concentration range. CER, alone and in combination with DON, increased the transcription of the autophagy related genes coding for the microtubule associated protein 1A/1B light chain 3 (LC3) and sequestome 1 (SQSTM1) as well as LC3 protein expression which was determined using immunocytochemistry. DON increased LC3 protein expression without induction of gene transcription, hence it seems plausible that CER and DON act on different pathways. The results support the hypothesis that CER induces autophagy via the LC3 pathway and damaged mitochondria are therefore eliminated. MDPI 2022-02-18 /pmc/articles/PMC8880806/ /pubmed/35202179 http://dx.doi.org/10.3390/toxins14020151 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Beisl, Julia
Pahlke, Gudrun
Ehling-Schulz, Monika
Del Favero, Giorgia
Marko, Doris
Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title_full Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title_fullStr Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title_full_unstemmed Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title_short Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells
title_sort cereulide and deoxynivalenol increase lc3 protein levels in hepg2 liver cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880806/
https://www.ncbi.nlm.nih.gov/pubmed/35202179
http://dx.doi.org/10.3390/toxins14020151
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