Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner

被引：701

作者：

Le Belle, Janel E. ^{[1
,2
]}

Orozco, Nicolas M. ^{[1
,2
]}

Paucar, Andres A. ^{[1
,2
]}

Saxe, Jonathan P. ^{[3
]}

Mottahedeh, Jack ^{[1
,2
]}

Pyle, April D. ^{[4
,5
,6
]}

Wu, Hong ^{[3
,5
,6
,7
]}

Kornblum, Harley I. ^{[1
,2
,3
,5
,6
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, NPI Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Med, Los Angeles, CA 90095 USA

来源：

CELL STEM CELL | 2011年 / 8卷 / 01期

基金：

美国国家卫生研究院;

关键词：

OLIGODENDROCYTE PRECURSOR CELLS; REACTIVE OXYGEN; REDOX REGULATION; DEPENDENT REGULATION; SUBVENTRICULAR ZONE; NADPH OXIDASES; PTEN; RECEPTOR; DIFFERENTIATION; BRAIN;

D O I：

10.1016/j.stem.2010.11.028

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function that may have significant implications for brain injury, disease, and repair.

引用

页码：59 / 71

页数：13

共 52 条

[1]

Vascular endothelial growth factor-mediated induction of manganese superoxide dismutase occurs through redox-dependent regulation of forkhead and IκB/NF-κB [J].