Over-expression of α-synuclein 98 triggers intracellular oxidative stress and enhances susceptibility to rotenone.
The α-synuclein protein is a major component of Lewy bodies found in the brains of patients with Parkinson's disease (PD). Recently, α-synuclein 98 (α-syn98), a small isoform of the wild type protein was isolated. The neurotoxicity of this protein was assessed by over-expressing α-syn98 in dopaminergic cells. Enhanced expression of α-syn98 was insufficient to adversely affect the survival of neurons or to promote aggregation of the protein. However, when exposed to rotenone, α-syn98 over-expressing dopaminergic cells demonstrated significantly increased cytotoxicity and aggregate formation. Furthermore, we found enhanced basal ROS production and MDA levels in α-syn98 over-expressing neurons. High basal oxidative stress induced by α-syn98, combined with oxidative stress caused by rotenone treatment, promoted aggregate formation and significantly decreased cell viability. These data indicate that α-syn98 can enhance the susceptibility of dopaminergic neurons to oxidative insults by raising steady-state levels of oxidative stress.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education), 1 Xiannongtan Street, Xuanwu District, Beijing 100050, PR China.
Kai-Li
KL
Ma
Yu-He
YH
Yuan
Lian-Kun
LK
Song
Ning
N
Han
Nai-Hong
NH
Chen
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D014475:Uncoupling Agents / Q000633:toxicity*; D051844:alpha-Synuclein / Q000096:biosynthesis*
D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D051844:alpha-Synuclein; D012402:Rotenone; D008315:Malondialdehyde