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Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese
Antagonistic interaction refers to opposing beneficial and adverse signaling by a single agent. Understanding opposing signaling is important because pathologic outcomes can result from adverse causative agents or the failure of beneficial mechanisms. To test for opposing responses at a systems leve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134992/ https://www.ncbi.nlm.nih.gov/pubmed/37107179 http://dx.doi.org/10.3390/antiox12040804 |
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author | Fernandes, Jolyn Uppal, Karan Liu, Ken H. Hu, Xin Orr, Michael Tran, ViLinh Go, Young-Mi Jones, Dean P. |
author_facet | Fernandes, Jolyn Uppal, Karan Liu, Ken H. Hu, Xin Orr, Michael Tran, ViLinh Go, Young-Mi Jones, Dean P. |
author_sort | Fernandes, Jolyn |
collection | PubMed |
description | Antagonistic interaction refers to opposing beneficial and adverse signaling by a single agent. Understanding opposing signaling is important because pathologic outcomes can result from adverse causative agents or the failure of beneficial mechanisms. To test for opposing responses at a systems level, we used a transcriptome–metabolome-wide association study (TMWAS) with the rationale that metabolite changes provide a phenotypic readout of gene expression, and gene expression provides a phenotypic readout of signaling metabolites. We incorporated measures of mitochondrial oxidative stress (mtOx) and oxygen consumption rate (mtOCR) with TMWAS of cells with varied manganese (Mn) concentration and found that adverse neuroinflammatory signaling and fatty acid metabolism were connected to mtOx, while beneficial ion transport and neurotransmitter metabolism were connected to mtOCR. Each community contained opposing transcriptome–metabolome interactions, which were linked to biologic functions. The results show that antagonistic interaction is a generalized cell systems response to mitochondrial ROS signaling. |
format | Online Article Text |
id | pubmed-10134992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101349922023-04-28 Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese Fernandes, Jolyn Uppal, Karan Liu, Ken H. Hu, Xin Orr, Michael Tran, ViLinh Go, Young-Mi Jones, Dean P. Antioxidants (Basel) Article Antagonistic interaction refers to opposing beneficial and adverse signaling by a single agent. Understanding opposing signaling is important because pathologic outcomes can result from adverse causative agents or the failure of beneficial mechanisms. To test for opposing responses at a systems level, we used a transcriptome–metabolome-wide association study (TMWAS) with the rationale that metabolite changes provide a phenotypic readout of gene expression, and gene expression provides a phenotypic readout of signaling metabolites. We incorporated measures of mitochondrial oxidative stress (mtOx) and oxygen consumption rate (mtOCR) with TMWAS of cells with varied manganese (Mn) concentration and found that adverse neuroinflammatory signaling and fatty acid metabolism were connected to mtOx, while beneficial ion transport and neurotransmitter metabolism were connected to mtOCR. Each community contained opposing transcriptome–metabolome interactions, which were linked to biologic functions. The results show that antagonistic interaction is a generalized cell systems response to mitochondrial ROS signaling. MDPI 2023-03-25 /pmc/articles/PMC10134992/ /pubmed/37107179 http://dx.doi.org/10.3390/antiox12040804 Text en © 2023 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 Fernandes, Jolyn Uppal, Karan Liu, Ken H. Hu, Xin Orr, Michael Tran, ViLinh Go, Young-Mi Jones, Dean P. Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title | Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title_full | Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title_fullStr | Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title_full_unstemmed | Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title_short | Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese |
title_sort | antagonistic interactions in mitochondria ros signaling responses to manganese |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134992/ https://www.ncbi.nlm.nih.gov/pubmed/37107179 http://dx.doi.org/10.3390/antiox12040804 |
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