Neurotrophins protect against cytosine arabinoside-induced apoptosis of immature rat cerebellar neurons

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.

参考文章(76)
Toru Nakazawa, Makoto Tamai, Nozomu Mori, Brain-derived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Investigative Ophthalmology & Visual Science. ,vol. 43, pp. 3319- 3326 ,(2002)
L Campos, JP Rouault, O Sabido, P Oriol, N Roubi, C Vasselon, E Archimbaud, JP Magaud, D Guyotat, High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy Blood. ,vol. 81, pp. 3091- 3096 ,(1993) , 10.1182/BLOOD.V81.11.3091.3091
Herbert M. Geller, Ke-Yi Cheng, Noriko K. Goldsmith, Alejandro A. Romero, Ai-Ling Zhang, Erick J. Morris, Lindsey Grandison, Oxidative stress mediates neuronal DNA damage and apoptosis in response to cytosine arabinoside. Journal of Neurochemistry. ,vol. 78, pp. 265- 275 ,(2001) , 10.1046/J.1471-4159.2001.00395.X
S Koizumi, ML Contreras, Y Matsuda, T Hama, P Lazarovici, G Guroff, K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells. The Journal of Neuroscience. ,vol. 8, pp. 715- 721 ,(1988) , 10.1523/JNEUROSCI.08-02-00715.1988
Irene E. Mazzoni, Farid A. Saı̈d, Raquel Aloyz, Freda D. Miller, David Kaplan, Ras Regulates Sympathetic Neuron Survival by Suppressing the p53-Mediated Cell Death Pathway The Journal of Neuroscience. ,vol. 19, pp. 9716- 9727 ,(1999) , 10.1523/JNEUROSCI.19-22-09716.1999
Pascal Meier, Andrew Finch, Gerard Evan, Apoptosis in development Nature. ,vol. 407, pp. 796- 801 ,(2000) , 10.1038/35037734
Ren-Wu Chen, Paul A. Saunders, Huafeng Wei, Zhuangwu Li, Prem Seth, De-Maw Chuang, Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and p53 in Neuronal Apoptosis: Evidence That GAPDH Is Upregulated by p53 The Journal of Neuroscience. ,vol. 19, pp. 9654- 9662 ,(1999) , 10.1523/JNEUROSCI.19-21-09654.1999
Frank J. GUNN-MOORE, Alan G. WILLIAMS, Nicholas J. TOMS, Jeremy M. TAVARÉ, Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated with cerebellar granule cell survival Biochemical Journal. ,vol. 324, pp. 365- 369 ,(1997) , 10.1042/BJ3240365