Document Detail


Neural stem/progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor-1alpha expression.
MedLine Citation:
PMID:  23410250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. Maintenance of NSPC multipotency is promoted by low oxygen tension, although the metabolic underpinnings of this trait have not been described. In this study, we investigated the metabolic state of undifferentiated NSPCs in culture, and tested their relative reliance on oxidative versus glycolytic metabolism for survival, as well as their dependence on hypoxia inducible factor-1alpha (HIF-1α) expression for maintenance of metabolic phenotype. Unlike primary neurons, NSPCs from embryonic and adult mice survived prolonged hypoxia in culture. In addition, NSPCs displayed greater susceptibility to glycolytic inhibition compared with primary neurons, even in the presence of alternative mitochondrial TCA substrates. NSPCs were also more resistant than neurons to mitochondrial cyanide toxicity, less capable of utilizing galactose as an alternative substrate to glucose, and more susceptible to pharmacological inhibition of the pentose phosphate pathway by 6-aminonicotinamide. Inducible deletion of exon 1 of the Hif1a gene improved the ability of NSPCs to utilize pyruvate during glycolytic inhibition, but did not alter other parameters of metabolism, including their ability to withstand prolonged hypoxia. Taken together, these data indicate that NSPCs have a relatively low requirement for oxidative metabolism for their survival and that hypoxic resistance is not dependent upon HIF-1α signaling.
Authors:
Kate M Candelario; C William Shuttleworth; Lee Anna Cunningham
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-11
Journal Detail:
Title:  Journal of neurochemistry     Volume:  125     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-06-20     Revised Date:  2014-01-08    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  420-9     Citation Subset:  IM    
Copyright Information:
© 2013 International Society for Neurochemistry.
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MeSH Terms
Descriptor/Qualifier:
6-Aminonicotinamide / pharmacology
Analysis of Variance
Animals
Bacterial Proteins / genetics
Cell Hypoxia / physiology*
Cell Survival / drug effects,  genetics
Cells, Cultured
Cerebral Cortex / cytology
Embryo, Mammalian
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Hypoxia-Inducible Factor 1, alpha Subunit / genetics,  metabolism*
Intermediate Filament Proteins / deficiency
L-Lactate Dehydrogenase / metabolism
Lactic Acid / metabolism
Luminescent Proteins / genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron, Transmission
Mitochondria / drug effects
Nerve Tissue Proteins / deficiency
Nestin
Neural Stem Cells / drug effects,  metabolism*,  ultrastructure
Oxygen / metabolism*
Phosphopyruvate Hydratase / metabolism
Pyruvic Acid / metabolism
Sodium Cyanide / pharmacology
Up-Regulation / drug effects,  genetics
Grant Support
ID/Acronym/Agency:
UL1 TR000041/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Enzyme Inhibitors; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Intermediate Filament Proteins; 0/Luminescent Proteins; 0/Nerve Tissue Proteins; 0/Nes protein, mouse; 0/Nestin; 0/yellow fluorescent protein, Bacteria; 329-89-5/6-Aminonicotinamide; 33X04XA5AT/Lactic Acid; 8558G7RUTR/Pyruvic Acid; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 4.2.1.11/Phosphopyruvate Hydratase; IY9XDZ35W2/Glucose; O5DDB9Z95G/Sodium Cyanide; S88TT14065/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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