Article

Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner.

NPI-Semel Institute for Neuroscience & Human Behavior and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell stem cell (Impact Factor: 22.15). 01/2011; 8(1):59-71. DOI: 10.1016/j.stem.2010.11.028
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
161 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondria are organelles derived from primitive symbiosis between archeon ancestors and prokaryotic α-proteobacteria species, which lost the capacity of synthetizing most proteins encoded the bacterial DNA, along the evolutionary process of eukaryotes. Nowadays, mitochondria are constituted by small circular mitochondrial DNA of 16 kb, responsible for the control of several proteins, including polypeptides of the electron transport chain. Throughout evolution, these organelles acquired the capacity of regulating energy production and metabolism, thus becoming central modulators of cell fate. In fact, mitochondria are crucial for a variety of cellular processes, including adenosine triphosphate production by oxidative phosphorylation, intracellular Ca(2+) homeostasis, generation of reactive oxygen species, and also cellular specialization in a variety of tissues that ultimately relies on specific mitochondrial specialization and maturation. In this review, we discuss recent evidence extending the importance of mitochondrial function and energy metabolism to the context of neuronal development and adult neurogenesis. © The Author(s) 2015.
    The Neuroscientist 05/2015; DOI:10.1177/1073858415585472 · 7.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the nervous system, ROS have been implicated in several physiological and pathological events. It has been suggested that the members of the family of the NADPH-oxidases (NOX) could be a source of ROS involved in many of these processes. In hippocampus, ROS produced by NOX are required for the NMDA receptor-dependent long-term potentiation (LTP), thereby regulating hippocampal synaptic plasticity and memory formation. In developing neurons, ROS regulate the dynamics of the axonal growth cone during the establishment of neuronal networks and, in neurons from Aplysia, ROS produced by NOX promote axonal growth. In addition, ROS produced by NOX critically influence the neuronal proliferation and neurogenesis and they have been implicated in the progression of the programmed cell death of neurons during cerebellar development. Most of the physiological and pathological actions of ROS are mediated by modification of the redox state of several proteins. The oxidation of these proteins occurs in specific amino acid residues such as cysteine, tyrosine and tryptophan. In particular, the oxidation of cysteine residues is a major mechanism for the control of several protein. These molecules include channels, enzymes and proteins from the cytoskeleton. For example, in the striatum, the hydrogen peroxide modulates dopamine release by the oxidation of the ATP-sensitive K+ channels and, in dorsal root ganglion neurons, ROS induce the growth cone collapse by the oxidation of CRMP2. It has been proposed that ROS also alter the redox state of the proteins of the signaling pathways. For example, ROS produced in response to growth factors control the proliferation and neurogenesis of neural precursor cells through the redox regulation of PI3K/Akt pathway. On the other hand, the oxidation of thioredoxins (Trx) and glutaredoxins (Grx1) leads to their dissociation from ASK1 that dephosphorylates and promotes its activation and the consequent stimulation of JNK and p38, which are involved in several physiological processes such as apoptosis. Other proteins such as thioredoxin-interacting protein (TXNIP) negatively regulates Trx1 and controls the cellular redox state. Finally, Akt has also been reported to be inactivated by direct oxidation, but it can also be activated by the oxidation of PTEN. In this chapter, we review the experimental evidences supporting a role for ROS in cell signaling in the nervous system and we discuss the interactions of ROS with several proteins as part of the mechanisms that regulates neuronal physiology.
    Reactive Oxygen Species, Lipid Peroxidation and Protein Oxidation, Edited by Angel Catalá, 09/2014: chapter Role of Reactive Oxygen Species As Signaling Molecules in the Regulation of Physiological Processes of the Nervous System: pages 169-204; Nova Science Publishers., ISBN: 978-1-63321-886-4
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although many features of neurogenesis during development and in the adult are intrinsic to the neurogenic cells themselves, the role of the microenvironment is irrefutable. The neurogenic niche is a melting pot of cells and factors that influence CNS development. How do the diverse elements assemble and when? How does the niche change structurally and functionally during embryogenesis and in adulthood? In this review, we focus on the impact of non-neural cells that participate in the neurogenic niche, highlighting how cells of different embryonic origins influence this critical germinal space. Copyright © 2015 Elsevier Inc. All rights reserved.

Full-text

Download
19 Downloads
Available from
May 21, 2014