Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells
Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells
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DOI：
10.1111/j.1471-4159.2010.07085.x
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发表时间：
2011-01-01
影响因子：
4.7
通讯作者：
Ientile, Riccardo
中科院分区：
文献类型：
--
作者：
Condello, Salvatore;Curro, Monica;Ientile, Riccardo
胍丁胺是一种内源性精氨酸代谢产物，被认为是一种新型的神经调节剂，在多种细胞损伤模型中对中枢神经系统起保护作用。然而，在神经退行性疾病中这些保护作用所涉及的机制知之甚少。本研究旨在探讨胍丁胺对帕金森病体内外模型中常用的鱼藤酮诱导的人多巴胺能神经母细胞瘤细胞株（SH-SY 5 Y）细胞损伤的影响。我们报告胍丁胺剂量依赖性抑制鱼藤酮诱导的细胞损伤，通过减少氧化应激。通过精胺获得类似的效果，表明这些化合物的清除作用。然而，与精胺不同，胍丁胺也阻止鱼藤酮诱导的核因子-κ B核转位和线粒体膜电位耗散。此外，鱼藤酮诱导的凋亡标志物，如caspase 3活性，Bax表达和细胞色素c释放的增加，与胍丁胺治疗显着衰减。这些研究结果表明，线粒体保护与胍丁胺在鱼藤酮模型的细胞凋亡的细胞死亡，胍丁胺的神经保护作用，因为抑制细胞凋亡信号机制出现。因此，胍丁胺可能通过保护多巴胺能神经元而具有治疗帕金森病的潜力。
P>Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in the CNS in several models of cellular damage. However, the mechanisms involved in these protective effects in neurodegenerative diseases are poorly understood. The present study was undertaken to investigate the effects of agmatine on cell injury induced by rotenone, commonly used in establishing in vivo and in vitro models of Parkinson's disease, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report that agmatine dose-dependently suppressed rotenone-induced cellular injury through a reduction of oxidative stress. Similar effects were obtained by spermine, suggesting a scavenging effect for these compounds. However, unlike spermine, agmatine also prevented rotenone-induced nuclear factor-kappa B nuclear translocation and mitochondrial membrane potential dissipation. Furthermore, rotenone-induced increase in apoptotic markers, such as caspase 3 activity, Bax expression and cytochrome c release, was significantly attenuated with agmatine treatment. These findings demonstrate mitochondrial preservation with agmatine in a rotenone model of apoptotic cell death, and that the neuroprotective action of agmatine appears because of suppressing apoptotic signalling mechanisms. Thus, agmatine may have therapeutic potential in the treatment of Parkinson's disease by protecting dopaminergic neurons.