Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells.
Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells.
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DOI：
10.1016/j.bbrc.2006.01.148
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发表时间：
2006-03
影响因子：
3.1
通讯作者：
Sheng-li Xu;M. Zhou;Shun Yu;Yanning Cai;A. Zhang;K. Uéda;P. Chan
中科院分区：
文献类型：
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作者：
Sheng-li Xu;M. Zhou;Shun Yu;Yanning Cai;A. Zhang;K. Uéda;P. Chan
越来越多的证据表明，氧化应激参与了神经元的退变，并能促进α-突触核蛋白的聚集。然而，α-突触核蛋白在生理和病理条件下的作用仍然知之甚少。在本研究中，我们研究了α-突触核蛋白与氧化应激之间可能的相互作用。在多巴胺能细胞系MES23.5中，我们发现200μM H_2O_2处理30min后，α-突触核蛋白从胞浆移位到胞核。用药后2小时，α-突触核蛋白在细胞核内的免疫活性增强。转移到细胞核的蛋白是α-突触核蛋白C末端的10 kDa片段，而全长α-突触核蛋白保留在细胞质中。硫黄素-S染色表明，细胞核中的C末端片段没有β-Sheet结构。我们目前的结果表明，200μM H_2O_2处理可诱导多巴胺能神经元α-突触核蛋白C末端片段在核内积聚，其作用有待进一步研究。
Growing evidence suggests that oxidative stress is involved in the neuronal degeneration and can promote the aggregation of α-synuclein. However, the role of α-synuclein under physiological and pathological conditions remains poorly understood. In the present study, we examined the possible interaction between the α-synuclein and oxidative stress. In a dopaminergic cell line MES23.5, we have found that the 200μM H2O2treatment induced the translocation of α-synuclein from cytoplasm to nuclei at 30min post-treatment. The immunoactivity of α-synuclein became highly intensive in the nuclei after 2h treatment. The protein translocated to nucleus was a 10kDa fragment of C-terminus region of α-synuclein, while full-length α-synuclein remained in cytoplasm. Thioflavine-S staining suggested that the C-terminal fragment in the nuclei has no β-sheet structures. Our present results indicated that 200μM H2O2treatment induces the intranuclear accumulation of the C-terminal fragment of α-synuclein in dopaminergic neurons, whose role remains to be investigated.