Hypoxia alters cell cycle regulatory protein expression and induces premature maturation of oligodendrocyte precursor cells.

Hypoxia alters cell cycle regulatory protein expression and induces premature maturation of oligodendrocyte precursor cells.
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DOI:
10.1371/journal.pone.0004739
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Rivkees SA
Rivkees SA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Akundi RS;Rivkees SA

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Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro. Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O2 or hypoxia (1% or 4% O2) for up to 7 days. We observed that 1% O2 lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor α (PDGFRα)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27Kip1 and phospho-cdc2, which play a role in OL differentiation, was seen as well. These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation.
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