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Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity

Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H(2)O(2) generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor mic...

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Autores principales: Bekeschus, Sander, Liebelt, Grit, Menz, Jonas, Singer, Debora, Wende, Kristian, Schmidt, Anke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783094/
https://www.ncbi.nlm.nih.gov/pubmed/35063803
http://dx.doi.org/10.1016/j.redox.2022.102234
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author Bekeschus, Sander
Liebelt, Grit
Menz, Jonas
Singer, Debora
Wende, Kristian
Schmidt, Anke
author_facet Bekeschus, Sander
Liebelt, Grit
Menz, Jonas
Singer, Debora
Wende, Kristian
Schmidt, Anke
author_sort Bekeschus, Sander
collection PubMed
description Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H(2)O(2) generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor microenvironment, e.g., hypoxia and ROS generation, has been associated with disease outcomes and therapeutic efficacy. Many reports have investigated the roles of the action of H(2)O(2) across many cell lines and disease models. The genes predisposing tumor cell lines to H(2)O(2)-mediated demise are less deciphered, however. To this end, we performed in-house transcriptional profiling of 35 cell lines and simultaneously investigated each cell line's H(2)O(2) inhibitory concentration (IC(25)) based on metabolic activity. More than 100-fold differences were observed between the most resistant and sensitive cell lines. Correlation and gene ontology pathway analysis identified a rigid association with genes intertwined in cell cycle progression and proliferation, as such functional categories dominated the top ten significant processes. The ten most substantially correlating genes (Spearman r > 0.70 or < -0.70) were validated using qPCR, showing complete congruency with microarray analysis findings. Western blotting confirmed the correlation of cell cycle-related proteins negatively correlating with H(2)O(2) IC(25). Top genes related to ROS production or antioxidant defense were only modest in correlation (Spearman r > 0.40 or < -0.40). In conclusion, our in-house transcriptomic correlation analysis revealed a set of cell cycle-associated genes associated with a priori resistance or sensitivity to H(2)O(2)-induced cellular demise with the detailed and causative roles of individual genes remaining unclear.
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spelling pubmed-87830942022-01-28 Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity Bekeschus, Sander Liebelt, Grit Menz, Jonas Singer, Debora Wende, Kristian Schmidt, Anke Redox Biol Research Paper Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H(2)O(2) generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor microenvironment, e.g., hypoxia and ROS generation, has been associated with disease outcomes and therapeutic efficacy. Many reports have investigated the roles of the action of H(2)O(2) across many cell lines and disease models. The genes predisposing tumor cell lines to H(2)O(2)-mediated demise are less deciphered, however. To this end, we performed in-house transcriptional profiling of 35 cell lines and simultaneously investigated each cell line's H(2)O(2) inhibitory concentration (IC(25)) based on metabolic activity. More than 100-fold differences were observed between the most resistant and sensitive cell lines. Correlation and gene ontology pathway analysis identified a rigid association with genes intertwined in cell cycle progression and proliferation, as such functional categories dominated the top ten significant processes. The ten most substantially correlating genes (Spearman r > 0.70 or < -0.70) were validated using qPCR, showing complete congruency with microarray analysis findings. Western blotting confirmed the correlation of cell cycle-related proteins negatively correlating with H(2)O(2) IC(25). Top genes related to ROS production or antioxidant defense were only modest in correlation (Spearman r > 0.40 or < -0.40). In conclusion, our in-house transcriptomic correlation analysis revealed a set of cell cycle-associated genes associated with a priori resistance or sensitivity to H(2)O(2)-induced cellular demise with the detailed and causative roles of individual genes remaining unclear. Elsevier 2022-01-17 /pmc/articles/PMC8783094/ /pubmed/35063803 http://dx.doi.org/10.1016/j.redox.2022.102234 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Bekeschus, Sander
Liebelt, Grit
Menz, Jonas
Singer, Debora
Wende, Kristian
Schmidt, Anke
Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title_full Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title_fullStr Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title_full_unstemmed Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title_short Cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
title_sort cell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783094/
https://www.ncbi.nlm.nih.gov/pubmed/35063803
http://dx.doi.org/10.1016/j.redox.2022.102234
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