Neurotoxicity Research

, 14:295

Dopamine induces supernumerary centrosomes and subsequent cell death through Cdk2 up-regulation in dopaminergic neuronal cells

Authors

  • Francisco J. Diaz-Corrales
    • Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
    • Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
  • Ikuko Miyazaki
    • Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
  • Ko Miyoshi
    • Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
  • Nobutaka Hattori
    • Department of NeurologyJuntendo University School of Medicine
  • Norio Ogawa
    • Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Article

DOI: 10.1007/BF03033854

Cite this article as:
Diaz-Corrales, F.J., Asanuma, M., Miyazaki, I. et al. neurotox res (2008) 14: 295. doi:10.1007/BF03033854

Abstract

Aggregation of proteins in the centrosome is implicated in the pathophysiology of Parkinson’s disease. However, the relevance of the centrosome in neurodegeneration is still obscure. Centrosome duplication is initiated by the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex. The present study determined changes in cyclin E or Cdk2 expression and in the cen-trosomal structure in dopaminergic neuronal CATH.a cells exposed to 50, 100 and 150 μM dopamine (DA) for 24 h. DA induced significant increase in Cdk2 protein and cyclin E protein, but not cyclin e mRNA. In DA-treated cells, the intense cyclin E- and Cdk2-immunofluorescence signals were co-localized around large and supernumerary centrosomes, and these two parameters of centrosome amplification were significantly increased compared with the control. Simultaneous co-treatment with DA and a Cdk2 inhibitor blocked centrosome amplification and enhanced cell viability. Our results demonstrated that DA could lead to cyclin E accumulation and Cdk2 up-regulation triggering supernumerary centrosomes and apoptotic cell death.

Keywords

CentrosomeCyclin-dependent kinase 2Cyclin EDopamineParkinson’s disease

Copyright information

© Springer 2008