TY  - JOUR
A1  - Müller, Niklas
A1  - Warwick, Timothy
A1  - Noack, Kurt
A1  - Malacarne, Pedro Felipe
A1  - Cooper, Arthur J. L.
A1  - Weißmann, Norbert
A1  - Schröder, Katrin
A1  - Brandes, Ralf
A1  - Rezende Felipe, Flávia Figueiredo de
T1  - Reactive oxygen species differentially modulate the metabolic and transcriptomic response of endothelial cells
T2  - Antioxidants
N2  - 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 µM or 300 µM), or menadione (5 µM) 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 µM 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 µM 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.
KW  - endothelial cells
KW  - metabolomics
KW  - RNAseq
KW  - reactive oxygen species
KW  - D-amino acid oxidase
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69288
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-692884
SN  - 2076-3921
N1  - The study was supported by the Deutsche Forschungsgemeinschaft (RE 4360/2-1 to FR; SFB815 to RPB; SFB834/3 TP A2 to RPB; SFB1039 to RPB, Excellent Cluster Cardio-Pulmonary Institute EXS2026), the Medicine Faculty of the Goethe University (Frankfurt, Germany); the German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Frankfurt.
VL  - 11
IS  - 2, art. 434
SP  - 1
EP  - 17
PB  - MDPI
CY  - Basel
ER  -