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Adult neural stem/progenitor cells reduce NMDA-induced excitotoxicity via the novel neuroprotective peptide pentinin.
- Source :
- Journal of Neurochemistry; May2009, Vol. 109 Issue 3, p858-866, 9p, 1 Color Photograph, 4 Graphs
- Publication Year :
- 2009
-
Abstract
- Although the potential of adult neural stem cells to repair damage via cell replacement has been widely reported, the ability of endogenous stem cells to positively modulate damage is less well studied. We investigated whether medium conditioned by adult hippocampal stem/progenitor cells altered the extent of excitotoxic cell death in hippocampal slice cultures. Conditioned medium significantly reduced cell death following 24 h of exposure to 10 μM NMDA. Neuroprotection was greater in the dentate gyrus, a region neighboring the subgranular zone where stem/progenitor cells reside compared with pyramidal cells of the cornis ammonis. Using mass spectrometric analysis of the conditioned medium, we identified a pentameric peptide fragment that corresponded to residues 26–30 of the insulin B chain which we termed ‘pentinin’. The peptide is a putative breakdown product of insulin, a constituent of the culture medium, and may be produced by insulin-degrading enzyme, an enzyme expressed by the stem/progenitor cells. In the presence of 100 pM of synthetic pentinin, the number of mature and immature neurons killed by NMDA-induced toxicity was significantly reduced in the dentate gyrus. These data suggest that progenitors in the subgranular zone may convert exogenous insulin into a peptide capable of protecting neighboring neurons from excitotoxic injury. [ABSTRACT FROM AUTHOR]
- Subjects :
- HYPOGLYCEMIC agents
NEURONS
NERVOUS system
CELL death
HIPPOCAMPUS (Brain)
Subjects
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 109
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37345218
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2009.06016.x