title: Multiple Ways of cfDNA Reception and Following ROS Production in Endothelial Cells.
abstract: Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels. We estimated that the activation of both TLR9 and other types of intracellular receptors initiates stress signaling in the endothelium independently. Signal transduction through these receptors activates NOX4 as the main source of ROS production in HUVECs.
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia. Annushka.f4g@gmail.com.
authors.forename: Anna Yu
authors.initials: AY
authors.lastname: Alekseeva
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Kameneva
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kostyuk
authors.affiliation: "Research Centre for Medical Genetics", Federal State Budgetary Institution, Moskvorechie str., 1, Moscow, 115478, Russia.
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Veiko
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D000099197:STING Protein
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D018168:Receptors, Retinoic Acid; D051217:Toll-Like Receptor 9; C410167:AIM2 protein, human; C437968:PLAAT4 protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C495371:TLR9 protein, human; C498910:NOX4 protein, human
keywords: Cardiovascular diseases; Cell-free DNA; DNA sensors; HUVECs; ROS