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Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor

Activation of the aryl hydrocarbon receptor (AHR) by the environmental toxin dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) causes diverse toxicities, including thymus atrophy and hepatosteatosis. The mechanisms by which AHR activation by TCDD leads to these toxicities are not fully understood....

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Autores principales: Diani-Moore, Silvia, Marques Pedro, Tiago, Rifkind, Arleen B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737989/
https://www.ncbi.nlm.nih.gov/pubmed/33320884
http://dx.doi.org/10.1371/journal.pone.0243842
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author Diani-Moore, Silvia
Marques Pedro, Tiago
Rifkind, Arleen B.
author_facet Diani-Moore, Silvia
Marques Pedro, Tiago
Rifkind, Arleen B.
author_sort Diani-Moore, Silvia
collection PubMed
description Activation of the aryl hydrocarbon receptor (AHR) by the environmental toxin dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) causes diverse toxicities, including thymus atrophy and hepatosteatosis. The mechanisms by which AHR activation by TCDD leads to these toxicities are not fully understood. Here we studied the effects of TCDD on a major energy pathway, glycolysis, using the chick embryo close to hatching, a well-established model for studying dioxin toxicity. We showed that 24 hr of TCDD treatment causes changes in glycolysis in both thymus and liver. In thymus glands, TCDD decreased mRNAs for glycolytic genes and glucose transporters, glycolytic indices and levels of IL7 mRNA, phosphorylated AKT (pAKT) and HIF1A, stimulators of glycolysis and promoters of survival and proliferation of thymic lymphocytes. In contrast, in liver, TCDD increased mRNA levels for glycolytic genes and glucose transporters, glycolytic endpoints and pAKT levels. Similarly, increases by TCDD in mRNA levels for glycolytic genes and glucose transporters in human primary hepatocytes showed that effects in chick embryo liver pertain also to human cells. Treatment with the glycolytic inhibitor 2-deoxy-d-glucose exacerbated the effects on thymus atrophy by TCDD, supporting a role for decreased glycolysis in thymus atrophy by TCDD, but did not prevent hepatosteatosis. NAD(+) precursors abolished TCDD effects on glycolytic endpoints in both thymus and liver. In summary, we report here that dioxin disrupts glycolysis mediated energy metabolism in both thymus and liver, and that it does so in opposite ways, decreasing it in the thymus and increasing it in the liver. Further, the findings support NAD(+) boosting as a strategy against metabolic effects of environmental pollutants such as dioxins.
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spelling pubmed-77379892021-01-08 Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor Diani-Moore, Silvia Marques Pedro, Tiago Rifkind, Arleen B. PLoS One Research Article Activation of the aryl hydrocarbon receptor (AHR) by the environmental toxin dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) causes diverse toxicities, including thymus atrophy and hepatosteatosis. The mechanisms by which AHR activation by TCDD leads to these toxicities are not fully understood. Here we studied the effects of TCDD on a major energy pathway, glycolysis, using the chick embryo close to hatching, a well-established model for studying dioxin toxicity. We showed that 24 hr of TCDD treatment causes changes in glycolysis in both thymus and liver. In thymus glands, TCDD decreased mRNAs for glycolytic genes and glucose transporters, glycolytic indices and levels of IL7 mRNA, phosphorylated AKT (pAKT) and HIF1A, stimulators of glycolysis and promoters of survival and proliferation of thymic lymphocytes. In contrast, in liver, TCDD increased mRNA levels for glycolytic genes and glucose transporters, glycolytic endpoints and pAKT levels. Similarly, increases by TCDD in mRNA levels for glycolytic genes and glucose transporters in human primary hepatocytes showed that effects in chick embryo liver pertain also to human cells. Treatment with the glycolytic inhibitor 2-deoxy-d-glucose exacerbated the effects on thymus atrophy by TCDD, supporting a role for decreased glycolysis in thymus atrophy by TCDD, but did not prevent hepatosteatosis. NAD(+) precursors abolished TCDD effects on glycolytic endpoints in both thymus and liver. In summary, we report here that dioxin disrupts glycolysis mediated energy metabolism in both thymus and liver, and that it does so in opposite ways, decreasing it in the thymus and increasing it in the liver. Further, the findings support NAD(+) boosting as a strategy against metabolic effects of environmental pollutants such as dioxins. Public Library of Science 2020-12-15 /pmc/articles/PMC7737989/ /pubmed/33320884 http://dx.doi.org/10.1371/journal.pone.0243842 Text en © 2020 Diani-Moore et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Diani-Moore, Silvia
Marques Pedro, Tiago
Rifkind, Arleen B.
Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title_full Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title_fullStr Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title_full_unstemmed Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title_short Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
title_sort organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737989/
https://www.ncbi.nlm.nih.gov/pubmed/33320884
http://dx.doi.org/10.1371/journal.pone.0243842
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