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  Reactive Oxygen Species Differentially Modulate the Metabolic and Transcriptomic Response of Endothelial Cells.

Muller, N., Warwick, T., Noack, K., Malacarne, P. F., Cooper, A. J. L., Weissmann, N., et al. (2022). Reactive Oxygen Species Differentially Modulate the Metabolic and Transcriptomic Response of Endothelial Cells. Antioxidants (Basel, Switzerland), 11(2), 434. doi:10.3390/antiox11020434.

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 Creators:
Muller, Niklas, Author
Warwick, Timothy1, Author              
Noack, Kurt, Author
Malacarne, Pedro Felipe, Author
Cooper, Arthur J L, Author
Weissmann, Norbert, Author
Schroder, Katrin, Author
Brandes, Ralf P, Author
Rezende, Flavia, Author
Affiliations:
1IMPRS, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_3242057              

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 Abstract: Reactive oxygen species (ROS) are important mediators of both physiological and pathophysiological signal transduction in the cardiovascular system. The effects of ROS on cellular processes depend on the concentration, localization, and duration of exposure. Cellular stress response mechanisms have evolved to mitigate the negative effects of acute oxidative stress. In this study, we investigate the short-term and long-term metabolic and transcriptomic response of human umbilical vein endothelial cells (HUVEC) to different types and concentrations of ROS. To generate intracellular H2O2, we utilized a lentiviral chemogenetic approach for overexpression of human D-amino acid oxidase (DAO). DAO converts D-amino acids into their corresponding imino acids and H2O2. HUVEC stably overexpressing DAO (DAO-HUVEC) were exposed to D-alanine (3 mM), exogenous H2O2 (10 M or 300 M), or menadione (5 M) for various timepoints and subjected to global untargeted metabolomics (LC-MS/MS) and RNAseq by MACE (Massive analysis of cDNA ends). A total of 300 M H2O2 led to pronounced changes on both the metabolic and transcriptomic level. In particular, metabolites linked to redox homeostasis, energy-generating pathways, and nucleotide metabolism were significantly altered. Furthermore, 300 M H2O2 affected genes related to the p53 pathway and cell cycle. In comparison, the effects of menadione and DAO-derived H2O2 mainly occurred at gene expression level. Collectively, all types of ROS led to subtle changes in the expression of ribosomal genes. Our results show that different types and concentration of ROS lead to a different metabolic and transcriptomic response in endothelial cells.

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 Dates: 2022-02-21
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: ISI: 35204316
DOI: 10.3390/antiox11020434
PMID: 35204316
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Title: Antioxidants (Basel, Switzerland)
Source Genre: Journal
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Pages: - Volume / Issue: 11 (2) Sequence Number: - Start / End Page: 434 Identifier: ISSN: 2076-3921