Neuromelanin enhances the toxicity of α-synuclein in SK-N-SH cells.
The key pathological feature of Parkinson's disease (PD) is selective degeneration of the neuromelanin (NM)-pigmented dopaminergic neurons in the substantia nigra (SN). NM, like other risk factors, such as oxidative stress (OS) and α-synuclein (α-syn), is involved in the pathogenesis of PD. But whether or not NM synergizes with α-syn or OS in the pathogenesis of PD remains unexplored. In the present study, we examined the effects of NM on cellular viability, apoptosis and free radical production in α-syn over-expressing human neuroblastoma cell line (SK-N-SH) in the presence or absence of the oxidizer Fenton's Reagent (FR). We showed that NM synergized with FR in suppressing cell viability, and in inducing apoptosis and hydroxyl radical production in all SK-N-SH cell lines. α-Syn over-expressing cells exhibited more pronounced effect, especially the A53T mutation. Our findings suggest that NM synergizes with both OS and α-syn in conferring dopaminergic vulnerability, adding to our understanding of the pathogenesis of PD.
Department of Psychiatry, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China. jieli@tijmu.edu.cn
Jie
J
Li
Junfeng
J
Yang
Peng
P
Zhao
Shen
S
Li
Renyun
R
Zhang
Xiaobin
X
Zhang
Dan
D
Liu
Benshu
B
Zhang
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008543:Melanins / Q000633:toxicity*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*
D004396:Coloring Agents; D008543:Melanins; D013778:Tetrazolium Salts; D013844:Thiazoles; D051844:alpha-Synuclein; C014121:neuromelanin; D017665:Hydroxyl Radical; D007501:Iron; C022616:thiazolyl blue