Parkin attenuates manganese-induced dopaminergic cell death

Youichirou Higashi, Masato Asanuma, Ikuko Miyazaki, Nobutaka Hattori, Yoshikuni Mizuno, Norio Ogawa

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)


Manganese as environmental factor is considered to cause parkinsonism and induce endoplasmic reticulum stress-mediated dopaminergic cell death. We examined the effects of manganese on parkin, identified as the gene responsible for familial Parkinson's disease, and the role of parkin in manganese-induced neuronal cell death. Manganese dose-dependently induced cell death of dopaminergic SH-SY5Y and CATH.a cells and cholinergic Neuro-2a cells, and that the former two cell types were more sensitive to manganese toxicity than Neuro-2a cells. Moreover, manganese increased the expression of endoplasmic reticulum stress-associated genes, including parkin, in SH-SY5Y cells and CATH.a cells, but not in Neuro-2a cells. Treatment with manganese resulted in accumulation of parkin protein in SH-SY5Y cells and its redistribution to the perinuclear region, especially aggregated Golgi complex, while in Neuro-2a cells neither expression nor redistribution of parkin was noted. Manganese showed no changes in proteasome activities in either cell. Transient transfection of parkin gene inhibited manganese- or manganese plus dopamine-induced cell death of SH-SY5Y cells, but not of Neuro-2a cells. Our results suggest that the attenuating effects of parkin against manganese- or manganese plus dopamine-induced cell death are dopaminergic cell-specific compensatory reactions associated with its accumulation and redistribution to perinuclear regions but not with proteasome system.

Original languageEnglish
Pages (from-to)1490-1497
Number of pages8
JournalJournal of Neurochemistry
Issue number6
Publication statusPublished - Jun 2004


  • Dopaminergic cell
  • Endoplasmic reticulum stress
  • Golgi complex
  • Manganese
  • Parkin
  • Proteasome

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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