作者: P LEEDS , Y LENG , E CHALECKAFRANASZEK , D CHUANG
DOI: 10.1016/J.NEUINT.2004.07.001
关键词:
摘要: Neurotrophin-induced neuroprotection against apoptosis was investigated using immature cultured cerebellar granule cells (CGC) from newborn rat pups. Apoptotic cell death induced by treatment with cytosine arabinoside (AraC) confirmed DNA fragmentation and quantified survival assays. AraC most effective in inducing when added to CGC on the day of culture preparation, while less or no effect observed at 24 48 h after plating, respectively. Pretreatment cultures for brain-derived neurotrophic factor (BDNF) neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3), robustly protected neurotoxicity. K252a, an inhibitor tropomyosin-related kinase (Trk) tyrosine receptor family which showed toxicity itself, blocked BDNF protection AraC-induced a concentration-dependent manner. Neither protein C activation nor inhibition mimicked affected BDNF, NT-3, caused marked, transient Akt through phosphatidylinositol (PI) 3-kinase. The neuroprotective effects were suppressed pretreatment LY 294002 (a PI 3-kinase inhibitor). also preceded mitogen activated (MAPK) two MAPK/ERK (MEK)-selective inhibitors, PD 98059 U-0126. Moreover, inhibitors MEK potentiated These results show that neurotrophins protect apoptosis, least part, TrkB-mediated 3-kinase/Akt signaling pathways.