Nakaso Kazuhiro, Ito Satoru, Nakashima Kenji
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishicho, Yonago, 683-8504, Japan.
Neurosci Lett. 2008 Feb 20;432(2):146-50. doi: 10.1016/j.neulet.2007.12.034. Epub 2007 Dec 23.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent epidemiological studies suggest that caffeine, one of the major components of coffee, has a protective effect against developing PD. However, the detailed mechanisms of how caffeine suppresses neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of caffeine using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. Caffeine prevented the apoptotic cell death induced by serum/retinoic acid (RA) deprivation, MPP+, rotenone, and 6-OHDA in SH-SY5Y cells in a dose dependent manner. Caffeine lowered caspase-3 activity induced by serum/RA deprivation and 6-OHDA administration, and also decreased the number of apoptotic condensed and/or fragmented nuclei. Akt was phosphorylated 60 min after caffeine administration in a dose dependent manner; PI3K inhibitors, wortmannin and LY294002 canceled this cytoprotective effect of caffeine. On the other hand, MAPKs such as Erk1/2, p38, or JNK were not activated by caffeine. These results suggest that caffeine has a cytoprotective effect due to the activation of the PI3K/Akt pathways in SH-SY5Y cells.
帕金森病（PD）是最常见的神经退行性疾病之一。近期流行病学研究表明，咖啡因作为咖啡的主要成分之一，对帕金森病的发展具有保护作用。然而，咖啡因抑制神经元死亡的详细机制尚未完全阐明。我们以人多巴胺能神经母细胞瘤SH-SY5Y细胞作为帕金森病模型，研究了咖啡因的细胞保护机制。咖啡因以剂量依赖的方式预防了血清/视黄酸（RA）剥夺、MPP +、鱼藤酮和6-OHDA诱导的SH-SY5Y细胞凋亡性细胞死亡。咖啡因降低了由血清/RA剥夺和6-OHDA给药诱导的半胱天冬酶-3活性，并减少了凋亡浓缩和/或碎片化细胞核的数量。咖啡因给药60分钟后，Akt以剂量依赖的方式被磷酸化；PI3K抑制剂渥曼青霉素和LY294002取消了咖啡因的这种细胞保护作用。另一方面，咖啡因未激活诸如Erk1/2、p38或JNK等丝裂原活化蛋白激酶（MAPKs）。这些结果表明，在SH-SY5Y细胞中，由于PI3K/Akt途径的激活，咖啡因具有细胞保护作用。
