Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells

Biochem Biophys Res Commun. 2006 Mar 31;342(1):330-5. doi: 10.1016/j.bbrc.2006.01.148. Epub 2006 Feb 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cell Survival / drug effects
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Dopamine / biosynthesis
  • Dopamine / metabolism*
  • Hydrogen Peroxide / pharmacology
  • Mice
  • Neurons / cytology*
  • Neurons / metabolism*
  • Oxidative Stress*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • Peptide Fragments
  • alpha-Synuclein
  • Hydrogen Peroxide
  • Dopamine