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Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we...

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Autores principales: Di, Rong, Zhang, Hanzhong, Lawton, Michael A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071042/
https://www.ncbi.nlm.nih.gov/pubmed/29954091
http://dx.doi.org/10.3390/toxins10070262
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author Di, Rong
Zhang, Hanzhong
Lawton, Michael A.
author_facet Di, Rong
Zhang, Hanzhong
Lawton, Michael A.
author_sort Di, Rong
collection PubMed
description Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we used the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to dissect the toxic effect of DON. Our results indicate that DON reduces the fecundity and lifespan of C. elegans. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis showed that DON upregulates innate immunity-related genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain-containing protein. Furthermore, our RNAseq data demonstrate that out of ~17,000 C. elegans genes, 313 are upregulated and 166 were downregulated by DON treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP-glucuronosyl transferase (UGTs) which are known to be involved in chemical detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26) and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28, respectively, are shown to contribute to DON tolerance by a RNAi bacterial feeding experiment. The results of this study provide insights to the targets of DON cytotoxicity and potential mitigation measures.
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spelling pubmed-60710422018-08-09 Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity Di, Rong Zhang, Hanzhong Lawton, Michael A. Toxins (Basel) Article Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we used the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to dissect the toxic effect of DON. Our results indicate that DON reduces the fecundity and lifespan of C. elegans. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis showed that DON upregulates innate immunity-related genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain-containing protein. Furthermore, our RNAseq data demonstrate that out of ~17,000 C. elegans genes, 313 are upregulated and 166 were downregulated by DON treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP-glucuronosyl transferase (UGTs) which are known to be involved in chemical detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26) and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28, respectively, are shown to contribute to DON tolerance by a RNAi bacterial feeding experiment. The results of this study provide insights to the targets of DON cytotoxicity and potential mitigation measures. MDPI 2018-06-27 /pmc/articles/PMC6071042/ /pubmed/29954091 http://dx.doi.org/10.3390/toxins10070262 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di, Rong
Zhang, Hanzhong
Lawton, Michael A.
Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title_full Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title_fullStr Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title_full_unstemmed Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title_short Transcriptome Analysis of C. elegans Reveals Novel Targets for DON Cytotoxicity
title_sort transcriptome analysis of c. elegans reveals novel targets for don cytotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071042/
https://www.ncbi.nlm.nih.gov/pubmed/29954091
http://dx.doi.org/10.3390/toxins10070262
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