title: Oxygen impairs oligodendroglial development via oxidative stress and reduced expression of HIF-1α.
abstract: The premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2. Influences of Hif-1α were investigated by Hif-1α luciferase reporter assays and Hif-1α-knockdown experiments. At 21% O2, cell proliferation was decreased and process arborization of OPCs was reduced. Expression of MBP, CNP, Olig1, Sox9 and Sox10 was lower at 21% O2, while Nrf2, SOD2, nitrotyrosine were increased. Apoptosis was unchanged. Luciferease reporter assay in OLN93 cells indicated increased Hif-1α activity at 5% O2. In OLN93 cells at 5% O2, Hif-1α knockdown decreased the expression of MBP and CNP, similar to that observed at 21% O2. These data indicate that culturing OPCs at 21% O2 negatively affects development and maturation. Both enhanced oxidative stress and reduced expression of Hif-1α-regulated genes contribute to these hyperoxia-induced changes.
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Brill
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.|Institute of Bioanalytics, University of Applied Sciences, Berlin, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Scheuer
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Endesfelder
authors.affiliation: Department of Neonatology, Charité University Medical Center, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C436006:Mbp protein, rat; D004676:Myelin Basic Protein; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C000627548:Sox9 protein, rat; C002744:3-nitrotyrosine; D014443:Tyrosine; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat; D010100:Oxygen