Oxygen impairs oligodendroglial development via oxidative stress and reduced expression of HIF-1α

被引:13
|
作者
Brill, Christina [1 ]
Scheuer, Till [1 ,2 ]
Buehrer, Christoph [1 ]
Endesfelder, Stefanie [1 ]
Schmitz, Thomas [1 ]
机构
[1] Charite, Dept Neonatol, Med Ctr, Berlin, Germany
[2] Univ Appl Sci, Inst Bioanalyt, Berlin, Germany
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
MESENCHYMAL STEM-CELLS; PRECURSOR CELLS; CNS PRECURSORS; HYPOXIA; PROLIFERATION; BRAIN; DIFFERENTIATION; MATURATION; MULTIPLE; SURVIVAL;
D O I
10.1038/srep43000
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1 alpha) 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-1 alpha were investigated by Hif-1 alpha luciferase reporter assays and Hif-1 alpha 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-1 alpha activity at 5% O2. In OLN93 cells at 5% O2, Hif-1 alpha 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-1 alpha-regulated genes contribute to these hyperoxia-induced changes.
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页数:14
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