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学科主题: 生命有机化学
题名: Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells
其他题名: 苯并内酰胺增加 SAPP 在两种细胞中的分泌作用
作者: Dolores lbarreta ; Miriam Duchen ; Ma DW(马大为) ; Qiao LX(乔立新) ; Alan P. Kozikowski ; Rene Etcheberrigaray
通讯作者: Rene Etcheberrigaray
刊名: NeuroReport
发表日期: 1999
卷: 10, 页:1035-1040
收录类别: SCI
部门归属: Laboratory of applied Neuroscience and Drug disocovery Program, Institute for Cognitive and Computational Sciences, The Research Building, WP14, Georgetown University Medical Center, 3970 Reservoir Road N.W, Washington, DC 20007, USA; 中国科学院上海有机化学研究所
英文摘要: Activation of protein kinase C is known to favor the α-secretase processing of the Alzheimer's disease (AD) amyloid precursor protein (APP), resulting in the generation of non-amyloidogenic soluble APP (sAPP0. Consequentyl, the relative secretion of amyloidogenic Aβ=1-40 and Aβ=1-42(3) is reduced. This is particularly relevant since fibroblasts and other cells ecpressing APP and presenilin AD mutations secrete increased amounts of total Aβ and/or increased ratios of Aβ=1-42(3)/Aβ=1-40. Interstingly, PKC defects have been found in AD brain (α and β isoforms) and in fibroblasts (α isoform) from AD patients. Here, we use a novel PKC activator (benzolactan, BL) with improced selectivity for the α,β and γ isoforms to enhance sAPP secretion if fibroblasts from AD patients and in PC12 cells. Incubation (2h) of AD fibroblasts with BL (1 and 10M) resulted in significant increases of sAPP secretion over basal level. sAPP secretion in BL-treated AD cells was also slightly higher compared to control BL--treated fibroblasts, which only showed significant increases of sAPP secretion after treatment with 10μM BL. Staurosporine (aPKC inhibitor) eliminated the effects of BL in both control and AD fibroblasts. BL and a related compound (LQ12) also caused and ~3-fold sAPP secretion in PC12PKC activator may prove useful to favor non-amyloidogenic APP processing and is,therefore, of potential therapectic alue.
语种: 英语
WOS记录号: WOS:000079904900028
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/15345
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
Dolores lbarreta,Miriam Duchen,Ma DW,et al. Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells[J]. NeuroReport,1999,10:1035-1040.
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