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RNA-Seq analysis implicates detoxification pathways in ovine mycotoxin resistance.

Zhang J, Pan Z, Moloney S, Sheppard A - PLoS ONE (2014)

Bottom Line: Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting from either an increase in levels of reactive oxygen species (ROS) above normal levels and/or the suppression of antioxidant protective pathways.Further, we present novel evidence for the amplification of Wnt signalling pathway activity in 'resistant' animals, resulting from the marked suppression of multiple key Wnt inhibitor genes.Notably, 'resistance' may be determined primarily by the ability of an individual to detoxify secondary metabolites generated by the metabolism of mycotoxins and the potentiation of Wnt signalling may be pivotal to achieving a favourable outcome upon challenge.

View Article: PubMed Central - PubMed

Affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand.

ABSTRACT
Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting from either an increase in levels of reactive oxygen species (ROS) above normal levels and/or the suppression of antioxidant protective pathways. However, few detailed molecular studies of mycotoxicoses in animals have been carried out. This study use current RNA-seq based approaches to investigate the effects of mycotoxin exposure in a ruminant model. Having first assembled a de novo reference transcriptome, we use RNA-Seq technology to define in vivo hepatic gene expression changes resulting from mycotoxin exposure in relationship to pathological effect. As expected, characteristic oxidative stress related gene expression is markedly different in animals exhibiting poorer outcomes. However, expression of multiple genes critical for detoxification, particularly members of the cytochrome P450 gene family, was significantly higher in animals exhibiting mycotoxin tolerance ('resistance'). Further, we present novel evidence for the amplification of Wnt signalling pathway activity in 'resistant' animals, resulting from the marked suppression of multiple key Wnt inhibitor genes. Notably, 'resistance' may be determined primarily by the ability of an individual to detoxify secondary metabolites generated by the metabolism of mycotoxins and the potentiation of Wnt signalling may be pivotal to achieving a favourable outcome upon challenge.

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KEGG pathways and their function groups.The left lane shows the pathway name; the right lane shows the involved genes number (right side of each column chart) and their percentage for all the associated genes in each pathway or term (upper of the figure). The different colours for column charts represent different pathway functional grouping based on Kappa score.
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pone-0099975-g005: KEGG pathways and their function groups.The left lane shows the pathway name; the right lane shows the involved genes number (right side of each column chart) and their percentage for all the associated genes in each pathway or term (upper of the figure). The different colours for column charts represent different pathway functional grouping based on Kappa score.

Mentions: For all the genes that differently expressed among groups, pathway enrichment analysis showed that a total number of 155 pathways were defined with at least one gene related to each pathway (File S2). To define the most significantly changed pathways, we primarily use the number of differentially expressed genes involved in each pathway as a standard. Focal adhesion, drug metabolism-cytochrome P450, and ECM-receptor interaction pathways are the three most significantly different biological roles thus identified. However, it is important to keep in mind that numbers of genes in each pathway are different. We additionally use the percentage change of known genes in each pathway as criterion. Caffeine metabolism, drug metabolism, and metabolism of xenobiotics by cytochrome P450 appear to be the top ones (Fig. 5). As for our study, the pathways of principle interest, namely detoxification and metabolism related pathways contain at least 4 differently expressed genes is listed in Table 9.


RNA-Seq analysis implicates detoxification pathways in ovine mycotoxin resistance.

Zhang J, Pan Z, Moloney S, Sheppard A - PLoS ONE (2014)

KEGG pathways and their function groups.The left lane shows the pathway name; the right lane shows the involved genes number (right side of each column chart) and their percentage for all the associated genes in each pathway or term (upper of the figure). The different colours for column charts represent different pathway functional grouping based on Kappa score.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061066&req=5

pone-0099975-g005: KEGG pathways and their function groups.The left lane shows the pathway name; the right lane shows the involved genes number (right side of each column chart) and their percentage for all the associated genes in each pathway or term (upper of the figure). The different colours for column charts represent different pathway functional grouping based on Kappa score.
Mentions: For all the genes that differently expressed among groups, pathway enrichment analysis showed that a total number of 155 pathways were defined with at least one gene related to each pathway (File S2). To define the most significantly changed pathways, we primarily use the number of differentially expressed genes involved in each pathway as a standard. Focal adhesion, drug metabolism-cytochrome P450, and ECM-receptor interaction pathways are the three most significantly different biological roles thus identified. However, it is important to keep in mind that numbers of genes in each pathway are different. We additionally use the percentage change of known genes in each pathway as criterion. Caffeine metabolism, drug metabolism, and metabolism of xenobiotics by cytochrome P450 appear to be the top ones (Fig. 5). As for our study, the pathways of principle interest, namely detoxification and metabolism related pathways contain at least 4 differently expressed genes is listed in Table 9.

Bottom Line: Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting from either an increase in levels of reactive oxygen species (ROS) above normal levels and/or the suppression of antioxidant protective pathways.Further, we present novel evidence for the amplification of Wnt signalling pathway activity in 'resistant' animals, resulting from the marked suppression of multiple key Wnt inhibitor genes.Notably, 'resistance' may be determined primarily by the ability of an individual to detoxify secondary metabolites generated by the metabolism of mycotoxins and the potentiation of Wnt signalling may be pivotal to achieving a favourable outcome upon challenge.

View Article: PubMed Central - PubMed

Affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand.

ABSTRACT
Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting from either an increase in levels of reactive oxygen species (ROS) above normal levels and/or the suppression of antioxidant protective pathways. However, few detailed molecular studies of mycotoxicoses in animals have been carried out. This study use current RNA-seq based approaches to investigate the effects of mycotoxin exposure in a ruminant model. Having first assembled a de novo reference transcriptome, we use RNA-Seq technology to define in vivo hepatic gene expression changes resulting from mycotoxin exposure in relationship to pathological effect. As expected, characteristic oxidative stress related gene expression is markedly different in animals exhibiting poorer outcomes. However, expression of multiple genes critical for detoxification, particularly members of the cytochrome P450 gene family, was significantly higher in animals exhibiting mycotoxin tolerance ('resistance'). Further, we present novel evidence for the amplification of Wnt signalling pathway activity in 'resistant' animals, resulting from the marked suppression of multiple key Wnt inhibitor genes. Notably, 'resistance' may be determined primarily by the ability of an individual to detoxify secondary metabolites generated by the metabolism of mycotoxins and the potentiation of Wnt signalling may be pivotal to achieving a favourable outcome upon challenge.

Show MeSH
Related in: MedlinePlus