Brain-derived neurotrophic factor inhibits cell cycle reentry but not endoplasmic reticulum stress in cultured neurons following oxidative or excitotoxic stress
| Autor: | J. Borg, François Lassablière, Evelyne Reynaud, Nadia Boutahar |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
N-Methylaspartate
Time Factors MAP Kinase Signaling System Biology Endoplasmic Reticulum Neuroprotection Cellular and Molecular Neuroscience Mice Phosphatidylinositol 3-Kinases Neurotrophic factors Stress Physiological Animals Brain-derived neurotrophic factor Cerebral Cortex Neurons Cell Death Endoplasmic reticulum Brain-Derived Neurotrophic Factor Cell Cycle Glutamate receptor Hydrogen Peroxide Cell biology Oxidative Stress nervous system biology.protein Unfolded protein response NMDA receptor Proto-Oncogene Proteins c-akt Neurotrophin |
| Zdroj: | Journal of neuroscience research. 88(10) |
| ISSN: | 1097-4547 |
| Popis: | Neurotrophins protect neurons against glutamate and oxidative stress, but the underlying mechanism remains unclear. We investigated the neuroprotective role of the neurotrophin brain-derived neurotrophic factor (BDNF) in neuronal cultures subjected to NMDA or H(2)O(2) toxicity and analyzed the molecular mechanisms involved, particularly those related to regulation of cell cycle or endoplasmic reticulum (ER) stress. Preincubation with BDNF of cortical neuron cultures prevented NMDA- or H(2)O(2)-induced neuronal death as well as MAPK-ERK1/2 activation. Inhibition of phosphatidylinositol 3-kinase (PI3-K) abolished the protective effect of BDNF. NMDA and H(2)O(2) induced activation of cell cycle reentry regulators such as retinoblastoma (Rb) protein and E2F1 transcription factor. However, BDNF abolished the activation of both factors. NMDA-induced expression of chaperone encoding gene BIP was slightly inhibited by BDNF, but it did not affect expression of ER stress protein CHOP. Our results suggest that BDNF neuroprotection may be mediated through inhibition of Ras-MAPK pathway and cell cycle reentry during oxidative or excitotoxic stress responses. However, BDNF did not modify expression of ER stress signal induced by NMDA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text