Common anti-apoptotic roles of parkin and α-synuclein in human dopaminergic cells

Yutaka Machida, Tomoki Chiba, Atsushi Takayanagi, Yoshikazu Tanaka, Masato Asanuma, Norio Ogawa, Akihiko Koyama, Takeshi Iwatsubo, Shosuke Ito, Poul Hening Jansen, Nobuyoshi Shimizu, Keiji Tanaka, Yoshikuni Mizuno, Nobutaka Hattori

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Abstract

Parkin, a product of the gene responsible for autosomal recessive juvenile parkinsonism (AR-JP), is an important player in the pathogenic process of Parkinson's disease (PD). Despite numerous studies including search for the substrate of parkin as an E3 ubiquitin-protein ligase, the mechanism by which loss-of-function of parkin induces selective dopaminergic neuronal death remains unclear. Related to this issue, here we show that antisense knockdown of parkin causes apoptotic cell death of human dopaminergic SH-SY5Y cells associated with caspase activation and accompanied by accumulation of oxidative dopamine (DA) metabolites due to auto-oxidation of DOPA and DA. Forced expression of α-synuclein (α-SN), another familial PD gene product, prevented accumulation of oxidative DOPA/DA metabolites and cell death caused by parkin loss. Our findings indicate that both parkin and α-SN share a common pathway in DA metabolism whose abnormality leads to accumulation of oxidative DA metabolites and subsequent cell death.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number1
DOIs
Publication statusPublished - 2005 Jun 24

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Keywords

  • Antisense
  • Apoptosis
  • Knockdown
  • Neuroblastoma
  • Parkin
  • Quinone
  • Synuclein dopamine metabolism

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Machida, Y., Chiba, T., Takayanagi, A., Tanaka, Y., Asanuma, M., Ogawa, N., Koyama, A., Iwatsubo, T., Ito, S., Jansen, P. H., Shimizu, N., Tanaka, K., Mizuno, Y., & Hattori, N. (2005). Common anti-apoptotic roles of parkin and α-synuclein in human dopaminergic cells. Biochemical and Biophysical Research Communications, 332(1), 233-240. https://doi.org/10.1016/j.bbrc.2005.04.124