Chetsawang Jirapa, Govitrapong Piyarat, Chetsawang Banthit
Department of Anatomy, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
J Pineal Res. 2007 Sep;43(2):115-20. doi: 10.1111/j.1600-079X.2007.00449.x.
Neurodegenerative diseases such as Parkinson's disease are illnesses associated with high morbidity and mortality with few, or no effective, options available for their treatment. In addition, the direct cause of selective dopaminergic cell loss in Parkinson's disease has not been clearly understood. Taken together, several studies have demonstrated that melatonin has a neuroprotective effect both in vivo and in vitro. Accordingly, the effects of melatonin on 1-methyl, 4-phenyl, pyridinium ion (MPP(+))-treated cultured human neuroblastoma SK-N-SH cell lines were investigated in the present study. The results showed that MPP(+) significantly decreased cell viability. By contrast, an induction of phosphorylation of c-Jun, activation of caspase-3 enzyme activity, cleavage of DNA fragmentation factors 45 and DNA fragmentation were observed in MPP(+)-treated cells. These changes were diminished by melatonin. These results demonstrate the cellular mechanisms of neuronal cell degeneration induced via c-Jun-N-terminal kinases and caspase-dependent signaling, and the potential role of melatonin on protection of neuronal cell death induced by this neurotoxin.
帕金森病等神经退行性疾病是发病率和死亡率都很高的疾病，治疗选择很少或根本没有有效的治疗方法。此外，帕金森病中选择性多巴胺能细胞丢失的直接原因尚未完全明确。综合来看，多项研究表明褪黑素在体内和体外均具有神经保护作用。因此，本研究探讨了褪黑素对经1-甲基-4-苯基吡啶离子（MPP(+)）处理的人神经母细胞瘤SK-N-SH细胞系的影响。结果显示，MPP(+)显著降低细胞活力。相比之下，在经MPP(+)处理的细胞中观察到c-Jun磷酸化的诱导、caspase-3酶活性的激活、DNA片段化因子45的切割和DNA片段化。这些变化被褪黑素减弱。这些结果证明了通过c-Jun氨基末端激酶和caspase依赖性信号传导诱导神经元细胞变性的细胞机制，以及褪黑素对这种神经毒素诱导的神经元细胞死亡的保护作用。
