Salsolinol, an endogenous neurotoxin, activates JNK and NF-kappaB signaling pathways in human neuroblastoma cells.
Salsolinol, an endogenous neurotoxin, activates JNK and NF-kappaB signaling pathways in human neuroblastoma cells.
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Salsolinol 是一种内源性神经毒素，可激活人神经母细胞瘤细胞中的 JNK 和 NF-kappaB 信号通路。
DOI：
10.1007/s11064-006-9246-0
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发表时间：
2007
影响因子：
4.4
通讯作者：
Ebadi,Manuchair
中科院分区：
文献类型：
--
作者：
Wanpen,Sawitri;Kooncumchoo,Patcharee;Shavali,Shaik;Govitrapong,Piyarat;Ebadi,Manuchair
沙龙醇是一种内源性神经毒素，与帕金森病(PD)的发病机制有关。在本研究中，我们研究了丹参素对人多巴胺能神经母细胞瘤SH-SY5Y细胞c-jun氨基末端激酶和核因子-κB(NF-κB)两种不同信号通路激活的影响。丹参素处理引起c-jun和c-jun磷酸化水平的上调。它还引起I-κBα的降解，并将活性的NF-κB移位到细胞核内。丹参酚能浓度依赖性地增强核因子-κB的结合活性。此外，丹参醇能降低抗凋亡蛋白Bcl2的水平，增加促凋亡蛋白Bax的表达，同时促进线粒体细胞色素-c的释放。丹参素处理组细胞线粒体复合体-I活性显著降低，活性氧(ROS)含量显著增加。这些结果部分表明，丹参素诱导的JNK和NF-κB信号通路可能参与诱导人多巴胺能神经元的凋亡，就像帕金森病一样。
Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson’s disease (PD). In the present study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun N-terminal kinase (JNK), and nuclear factor-κB, (NF-κB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IκBα and translocated the active NF-κB into the nucleus. The binding activity of NF-κB to DNA was enhanced by salsolinol in a concentration dependent manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein Bax, while enhancing the release of cytochrome-cfrom mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-κB signaling pathways may be involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson’s disease.