Parkin Cleaves Intracellular α-Synuclein Inclusions via the Activation of Calpain

Se Jung Kim, Jee Young Sung, Ji Won Um, Nobutaka Hattori, Yoshikuni Mizuno, Keiji Tanaka, Seung R. Paik, Jongsun Kim, Kwang Chul Chung

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60 Citations (Scopus)

Abstract

Mutations in the α-synuclein and parkin genes cause heritable forms of Parkinson's disease. In the present study, we examined the possible functional relationship between the parkin and α-synuclein genes in a conditionally immortalized embryonic hippocampal cell (H19-7) line. Whereas transient transfection of α-synuclein into neuronal H19-7 cells caused the formation of its intracytoplasmic inclusions and a significant cell death, the combined overexpression of parkin restored the α-synuclein-induced decrease in cell viability to control levels. In addition, the overexpression of parkin was found to generate selective cleavage of α-synuclein. Furthermore, the cytoprotective effect of parkin on α-synuclein-induced cell death was not inhibited in the presence of a proteasome inhibitor. Interestingly, the overexpression of parkin induced the activation of an intracellular cysteine protease, calpain, but not caspase, and the cytoprotective effect of parkin on α-synuclein cytotoxicity was significantly inhibited by the presence of calpain-specific inhibitors. In conclusion, our results suggest that parkin accelerates the degradation of α-synuclein via the activation of the nonproteasomal protease, calpain, leading to the prevention of α-synuclein-induced cell death in embryonic hippocampal progenitor cells.

Original languageEnglish
Pages (from-to)41890-41899
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
Publication statusPublished - 2003 Oct 24

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kim, S. J., Sung, J. Y., Um, J. W., Hattori, N., Mizuno, Y., Tanaka, K., Paik, S. R., Kim, J., & Chung, K. C. (2003). Parkin Cleaves Intracellular α-Synuclein Inclusions via the Activation of Calpain. Journal of Biological Chemistry, 278(43), 41890-41899. https://doi.org/10.1074/jbc.M306017200