International journal of molecular sciences, 2021-10, Vol.22 (21), p.11646
2021
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- Autor(en) / Beteiligte
- Titel
- Constitutive Oxidative Stress by SEPHS1 Deficiency Induces Endothelial Cell Dysfunction
- Ist Teil von
- International journal of molecular sciences, 2021-10, Vol.22 (21), p.11646
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in -knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. -knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in -knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms222111646Titel-ID: cdi_doaj_primary_oai_doaj_org_article_fcf946c74f184f6fa9cbf931ace7d468
- Format
- –
- Schlagworte
- Amino acids, Angiogenesis, Animals, Cancer, Cell growth, Cell Line, Cell proliferation, Cloning, DNA damage, Embryos, endothelial cell, Endothelial cells, Endothelial Cells - metabolism, Endothelial Cells - pathology, Enzymes, Eukaryotes, Gene Deletion, Gene Knockout Techniques, HEK293 Cells, Humans, Insects, Isoforms, Lipid Peroxidation, Lipids, Mammals, Mice, Morphology, Mutation, NAD(P)H oxidase, Nitric oxide, Oxidative Stress, Phosphotransferases - genetics, Phosphotransferases - metabolism, Reactive Nitrogen Species - genetics, Reactive Nitrogen Species - metabolism, reactive oxygen species, Selenium, Selenocysteine, Selenophosphate, selenophosphate synthetase, selenoprotein, Superoxide dismutase, Superoxides - metabolism, Xanthine oxidase