Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells.
Growing evidence suggests that oxidative stress is involved in the neuronal degeneration and can promote the aggregation of alpha-synuclein. However, the role of alpha-synuclein under physiological and pathological conditions remains poorly understood. In the present study, we examined the possible interaction between the alpha-synuclein and oxidative stress. In a dopaminergic cell line MES23.5, we have found that the 200microM H(2)O(2) treatment induced the translocation of alpha-synuclein from cytoplasm to nuclei at 30min post-treatment. The immunoactivity of alpha-synuclein became highly intensive in the nuclei after 2h treatment. The protein translocated to nucleus was a 10kDa fragment of C-terminus region of alpha-synuclein, while full-length alpha-synuclein remained in cytoplasm. Thioflavine-S staining suggested that the C-terminal fragment in the nuclei has no beta-sheet structures. Our present results indicated that 200microM H(2)O(2) treatment induces the intranuclear accumulation of the C-terminal fragment of alpha-synuclein in dopaminergic neurons, whose role remains to be investigated.
Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative diseases, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China.
Shengli
S
Xu
Ming
M
Zhou
Shun
S
Yu
Yanning
Y
Cai
Alex
A
Zhang
Kenji
K
Uéda
Piu
P
Chan
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D010446:Peptide Fragments; D051844:alpha-Synuclein; D006861:Hydrogen Peroxide; D004298:Dopamine