| First Author | Qin XY | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 11 | Pages | e112996 |
| PubMed ID | 25426952 | Mgi Jnum | J:225276 |
| Mgi Id | MGI:5692340 | Doi | 10.1371/journal.pone.0112996 |
| Citation | Qin XY, et al. (2014) carboxypeptidase E-DeltaN, a neuroprotein transiently expressed during development protects embryonic neurons against glutamate neurotoxicity. PLoS One 9(11):e112996 |
| abstractText | Neuroprotective proteins expressed in the fetus play a critical role during early embryonic neurodevelopment, especially during maternal exposure to alcohol and drugs that cause stress, glutamate neuroexcitotoxicity, and damage to the fetal brain, if prolonged. We have identified a novel protein, carboxypeptidase E-DeltaN (CPE-DeltaN), which is a splice variant of CPE that has neuroprotective effects on embryonic neurons. CPE-DeltaN is transiently expressed in mouse embryos from embryonic day 5.5 to postnatal day 1. It is expressed in embryonic neurons, but not in 3 week or older mouse brains, suggesting a function primarily in utero. CPE-DeltaN expression was up-regulated in embryonic hippocampal neurons in response to dexamethasone treatment. CPE-DeltaN transduced into rat embryonic cortical and hippocampal neurons protected them from glutamate- and H2O2-induced cell death. When transduced into embryonic cortical neurons, CPE-DeltaN was found in the nucleus and enhanced the transcription of FGF2 mRNA. Embryonic cortical neurons challenged with glutamate resulted in attenuated FGF2 levels and cell death, but CPE-DeltaN transduced neurons treated in the same manner showed increased FGF2 expression and normal viability. This neuroprotective effect of CPE-DeltaN was mediated by secreted FGF2. Through receptor signaling, FGF2 activated the AKT and ERK signaling pathways, which in turn increased BCL-2 expression. This led to inhibition of caspase-3 activity and cell survival. |
