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

研究成果: Article査読

63 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)233-240
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
332
1
DOI
出版ステータスPublished - 2005 6月 24
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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