期刊
NEUROSCIENCE
卷 169, 期 4, 页码 1840-1847出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2010.05.069
关键词
anandamide; N-stearoyltyrosine; A beta; MAPK; apoptosis
资金
- National Natural Science Founding of China [30672441, 30701018, 30873057]
- Shanghai Municipal Science and Technology Commission [08JC1413600]
- Shanghai Municipal Education Committee [J50201]
- Foundation of Ministry of Education of China [20050266003, 20070248067]
N-stearoyltyrosine (NsTyr), an anandamide (AEA) analogue is similar to AEA not only structurally but also in terms of biological activity. Since A beta-induced neuronal injury triggers the activation of mitogen-activated protein kinase (MAPK) pathways and the induction or activation of pro- and anti-apoptotic proteins, in the present study we aimed to assess the protective effect of NsTyr against A beta induced neuronal apoptosis. Cell viability and neuronal injury were respectively measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Hoechst staining and flow cytometric assessment were used to evaluate cell apoptosis. The antiapoptotic mechanism involved MAPK phosphoryation and Bcl-2/Bax expression was investigated. The best neuroprotective effect on A beta 25-35-induced neuronal apoptosis was observed in the presence of NsTyr (1 mu M). NsTyr exerted anti-apoptotic effect at least partly via activating p-ERK-Bcl-2 but suppressing p-p38-Bax pathways. Moreover a dynamic balance between p-ERK and p-p38 MAPK pathways in NsTyr-induced neuronal protection suggested an interaction between them. Our results indicated the neuroprotective effect of NsTyr on A beta 25-35-induced neuronal injury was at least partly due to anti-apoptosis and raised the possibility that NsTyr might reduce neurodegenerative disorders. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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