The Role of Alpha-Synuclein in Melanin Synthesis in Melanoma and Dopaminergic Neuronal Cells

نویسندگان

  • Tianhong Pan
  • Julie Zhu
  • Wen-Jen Hwu
  • Joseph Jankovic
چکیده

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 (α-Syn) that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that α-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 α-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 determined effects of α-Syn on melanin synthesis. Our results showed that UVB light exposure increased melanin synthesis in all 4 cell lines. However, we found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells. Different from melanoma cells, the melanin content was higher in α-Syn-over-expressed dopaminergic neuronal SH-SY5Y and PC12 cells, cellular models of PD, than that in non-α-Syn-expressed control cells. We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in melanoma cells and in dopaminergic neuronal cells.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Evaluation of antioxidant and anti-melanogenic activities of different extracts from aerial parts of Nepeta binaludensis Jamzad in murine melanoma B16F10 cells

Objective(s): Nepeta binaludensis Jamzad (Lamiaceae) has been used in folk medicine of Iran to cure various diseases. The plant is an endemic species to the country that has recently been identified in Razavi Khorasan province. To evaluate the antioxidant and anti-melanogenesis of N. binaludensis, in this study the inhibitory activity of different extracts of N. binaludensis in murine melanoma ...

متن کامل

Alpha-synuclein induced apoptosis and proliferation interacted with CD44 in human lymphocytes

Human ?-synuclein is a 140 amino acid protein with little or no secondary structure. The ?-synuclein is expressed at high levels in the brain and enriched in neural synaptic terminals but its physiological function remains largely unknown. More recently, ?-synuclein has been shown to be one of the principal componets of Lewy bodies, neuronal inclusions that are found in diverse human neurodegen...

متن کامل

Alpha-synuclein induced apoptosis and proliferation interacted with CD44 in human lymphocytes

Human ?-synuclein is a 140 amino acid protein with little or no secondary structure. The ?-synuclein is expressed at high levels in the brain and enriched in neural synaptic terminals but its physiological function remains largely unknown. More recently, ?-synuclein has been shown to be one of the principal componets of Lewy bodies, neuronal inclusions that are found in diverse human neurodegen...

متن کامل

Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells.

alpha-Synuclein is an abundant presynaptic protein implicated in neuronal plasticity and neurodegenerative diseases. Although the function of alpha-synuclein is not thoroughly elucidated, we found that alpha-synuclein regulates dopamine synthesis by binding to and inhibiting tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. Understanding alpha-synuclein function in dopaminer...

متن کامل

Clioquinol-induced ordered conformational behavior in alpha-synuclein: promising relevance for therapeutic approach to Parkinson's disease

Parkinson?¦s disease (PD) is a devastating and an intricate complex neurological disorder that results from the progressive degeneration of nerve cells in Substantia nigra that controls movement. The pathological hallmark of PD is the formation of insoluble protein aggregates known as lewey bodies. Alpha-synuclein is the major constituent of these fibrillar structures. Alpha-synuclein a 140 ami...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2012