Effects of a verbenachalcone derivative on neurite outgrowth, inhibition of caspase induction and gene expression
Effects of a verbenachalcone derivative on neurite outgrowth, inhibition of caspase induction and gene expression
复制标题
DOI：
10.1016/j.bmcl.2004.12.001
复制
发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Cuny, GD
中科院分区：
文献类型：
--
作者：
Yeh, LA;Padmanaban, D;Cuny, GD
合成了马鞭草查尔酮衍生物，并显示其保护N2 a细胞免受血清饥饿引起的半胱天冬酶诱导，并增强NGF对PC 12细胞中神经突生长的影响。作为化合物作用机制的初步研究，我们使用寡核苷酸（类似于10,000个基因探针）微阵列在PC 12细胞中进行差异基因表达谱分析。在NGF（2和50 ng/mL）和NGF（2 ng/mL）加马鞭草查尔酮衍生物的存在下比较基因表达模式。在化合物存在下，10个基因显著（大于或等于2倍; p小于或等于0.05）上调，7个基因显著下调。这些结果通过定量实时PCR对一组基因（组织蛋白酶L、sigma-1受体和蛋白酪氨酸磷酸酶受体R型）进行了独立验证。这些基因或它们的蛋白质产物可能代表用于治疗神经变性（例如阿尔茨海默病）的有用的治疗靶点。(C)2004爱思唯尔有限公司保留所有权利。
A verbenachalcone derivative was synthesized and shown to protect N2a cells from caspase induction caused by serum starvation and to enhance the effect of NGF on neurite outgrowth in PC12 cells. As an initial investigation of the compound's mechanism(s) of action, we performed differential gene expression profiling in PC12 cells using oligonucleotide (similar to10,000 gene probes) microarrays. Gene expression patterns were compared in the presence of NGF (2 and 50 ng/mL) and NGF (2 ng/mL) plus the verbenachalcone derivative. Ten genes were significantly (greater than or equal to 2-fold; p less than or equal to 0.05) up-regulated and seven genes were significantly down-regulated in the presence of the compound. These results were independently validated by quantitative real-time PCR for a subset of genes (cathepsin L, sigma-1 receptor and protein tyrosine phosphatase receptor type R). These genes or their protein products may represent useful therapeutic targets for treating neurodegeneration, such as Alzheimer's disease. (C) 2004 Elsevier Ltd. All rights reserved.