the role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cellsα-突触核蛋白在黑色素合成黑色素瘤的作用,多巴胺能神经细胞.pdfVIP

The Role of Alpha-Synuclein in Melanin Synthesis in Melanoma and Dopaminergic Neuronal Cells 1 1 2 1,3 Tianhong Pan *, Julie Zhu , Wen-Jen Hwu , Joseph Jankovic 1 Neurology Department, Parkinson Disease Research Laboratory, Baylor College of Medicine, Houston, Texas, United States of America, 2 Melanoma Medical Oncology, M.D. Anderson Cancer Center, Houston, Texas, United States of America, 3 Parkinson’s Disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, Texas, United States of America Abstract The relatively high co-occurrence of Parkinson’s disease (PD) and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR)- induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM), the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD. SNCA is a PD-causing gene coding for alpha- Synuclein (a-Syn) that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that a-Syn can interact with tyrosinase (TYR) and inhibit tyrosine hydroxylase (TH), both of which are enzymes involved in the biosynthesis of melanin and dopamine (DA), led us to propose that a-Syn may participate in the regulation of melanin synthesis. In this study, by applying ultraviolet B (UVB) light, a physiologically relevant stimulus of melanogenesis, we detected melanin synthesis in A375 and SK-MEL-28 melanoma cells and in SH-SY5Y and PC12 dopaminergic neuronal cells and determi