Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):147-51. doi: 10.1016/j.bbrc.2009.11.022. Epub 2009 Nov 10.
The selective loss of dopaminergic neurons in the substantia nigra pars compacta is a feature of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity is the most common experimental model used to investigate the pathogenesis of PD. Administration of MPTP in mice produces neuropathological defects as observed in PD and 1-methyl-4-pyridinium (MPP(+)) induces cell death when neuronal cell cultures are used. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. In the present study, we demonstrated that AMPK is activated by MPTP in mice and MPP(+) in SH-SY5Y cells. The inhibition of AMPK by compound C resulted in an increase in MPP(+)-induced cell death. We further showed that overexpression of AMPK increased cell viability after exposure to MPP(+) in SH-SY5Y cells. Based on these results, we suggest that activation of AMPK might prevent neuronal cell death and play a role as a survival factor in PD.
黑质致密部多巴胺能神经元的选择性丧失是帕金森病（PD）的一个特征。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的神经毒性是研究 PD 发病机制最常用的实验模型。在小鼠中给予 MPTP 会产生与 PD 观察到的神经病理学缺陷，而当使用神经元细胞培养物时，1-甲基-4-吡啶鎓（MPP(+））会诱导细胞死亡。AMP 激活的蛋白激酶（AMPK）是能量稳态的关键调节剂。在本研究中，我们证明了 MPTP 在小鼠中和 MPP(+)在 SH-SY5Y 细胞中激活 AMPK。用化合物 C 抑制 AMPK 会导致 MPP(+)诱导的细胞死亡增加。我们进一步表明，在 SH-SY5Y 细胞中暴露于 MPP(+)后，过表达 AMPK 会增加细胞活力。基于这些结果，我们认为激活 AMPK 可能防止神经元细胞死亡，并在 PD 中发挥生存因子的作用。
