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

57 引用 (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.

元の言語English
ページ(範囲)233-240
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
332
発行部数1
DOI
出版物ステータスPublished - 2005 6 24

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Synucleins
Dopamine
Cell death
Metabolites
Cell Death
Parkinson Disease
Genes
Ubiquitin-Protein Ligases
Parkinsonian Disorders
Caspases
Metabolism
Chemical activation
Oxidation
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

これを引用

Machida, Y., Chiba, T., Takayanagi, A., Tanaka, Y., Asanuma, M., Ogawa, N., ... 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

Common anti-apoptotic roles of parkin and α-synuclein in human dopaminergic cells. / Machida, Yutaka; Chiba, Tomoki; Takayanagi, Atsushi; Tanaka, Yoshikazu; Asanuma, Masato; Ogawa, Norio; Koyama, Akihiko; Iwatsubo, Takeshi; Ito, Shosuke; Jansen, Poul Hening; Shimizu, Nobuyoshi; Tanaka, Keiji; Mizuno, Yoshikuni; Hattori, Nobutaka.

:: Biochemical and Biophysical Research Communications, 巻 332, 番号 1, 24.06.2005, p. 233-240.

研究成果: Article

Machida, Y, Chiba, T, Takayanagi, A, Tanaka, Y, Asanuma, M, Ogawa, N, Koyama, A, Iwatsubo, T, Ito, S, Jansen, PH, 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, 巻. 332, 番号 1, pp. 233-240. https://doi.org/10.1016/j.bbrc.2005.04.124
Machida, Yutaka ; Chiba, Tomoki ; Takayanagi, Atsushi ; Tanaka, Yoshikazu ; Asanuma, Masato ; Ogawa, Norio ; Koyama, Akihiko ; Iwatsubo, Takeshi ; Ito, Shosuke ; Jansen, Poul Hening ; Shimizu, Nobuyoshi ; Tanaka, Keiji ; Mizuno, Yoshikuni ; Hattori, Nobutaka. / Common anti-apoptotic roles of parkin and α-synuclein in human dopaminergic cells. :: Biochemical and Biophysical Research Communications. 2005 ; 巻 332, 番号 1. pp. 233-240.
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