A synthetic analog of verbenachalcone potentiates NGF-induced neurite outgrowth and enhances cell survival in neuronal cell models.
A synthetic analog of verbenachalcone potentiates NGF-induced neurite outgrowth and enhances cell survival in neuronal cell models.
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DOI：
10.1016/j.neulet.2009.05.010
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发表时间：
2009-08-14
影响因子：
2.5
通讯作者：
Ibeanu GC
中科院分区：
文献类型：
--
作者：
Clement CM;Dandepally SR;Williams AL;Ibeanu GC
本研究使用嗜铬细胞瘤（PC12）细胞的衍生物NeuroScreen-1 （NS-1）细胞来检测一种新型合成马鞭草甲酮衍生物DSRB20-022 （C22）诱导的神经突生长。我们用不同浓度的C22在2ng/mL神经生长因子（NGF）存在下处理NS-1细胞。C22在2 μM及以上浓度下具有剂量依赖性，显著增强NS-1细胞中ngf依赖性神经突的生长。在缺乏NGF的情况下，C22不表现出神经生成活性，但在不诱导细胞毒性的情况下，促进了神经突细胞的浓度依赖性增加。细胞活力测定显示，C22及其亲本化合物马鞭草甲素（VC）对NS-1、PC12和小鼠神经2a （N2a）细胞株具有神经保护作用，并能提高其在血清剥夺条件下的存活率。结果表明，C22对NS-1中ngf诱导的神经突生长的增强依赖于MAP激酶。此外，C22和VC的神经保护作用伴随着抑制caspase-3/7的激活。然而，C22和VC对caspase 3/7激活的拮抗作用可能通过不同的作用机制发挥。
This study uses NeuroScreen-1 (NS-1) cells, a derivative of pheochromocytoma (PC12) cells, to examine neurite outgrowth induced by a novel synthetic verbenachalcone derivative, DSRB20-022 (C22). We treated NS-1 cells with varying concentrations of C22 in the presence of 2ng/mL nerve growth factor (NGF). A dose dependent effect of C22 was observed at concentrations of 2 μM and above, resulting in significant enhancement of NGF-dependent neurite outgrowth in NS-1 cells. C22 did not exhibit neuritogenic activity in the absence of NGF, but promoted a concentration-dependent increase in neurite-bearing cells without inducing cytotoxicity. Cell viability assays showed that C22 and the parent compound verbenachalcone (VC) are neuroprotective and enhanced survival of NS-1, PC12, and the murine neuro-2A (N2a) cell lines under conditions of serum deprivation. The results show that augmentation of NGF-induced neurite outgrowth by C22 in NS-1 was dependent on MAP kinase. Furthermore, the neuroprotective function of C22 and VC was accompanied by suppression of caspase-3/7 activation. However, C22 and VC exerted their antagonistic effects on caspase 3/7 activation through potentially different mechanisms of action.
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影响因子：
7.2
作者：
Kueenzi, Peter;Kiefer, Sabine;Hamburger, Matthias
通讯作者：
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影响因子：
3.5
作者：
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影响因子：
3.5
作者：
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影响因子：
2.1
作者：
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通讯作者：
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影响因子：
2.7
作者：
Yeh, LA;Padmanaban, D;Cuny, GD
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Cuny, GD