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Neurochemical Research

, Volume 30, Issue 6–7, pp 839–845 | Cite as

Puma and p53 Play Required Roles in Death Evoked in a Cellular Model of Parkinson Disease

  • Subhas C. Biswas
  • Elizabeth Ryu
  • Clara Park
  • Cristina Malagelada
  • Lloyd A. Greene
Article

Abstract

6-Hydroxydopamine (6-OHDA) is widely used in vivo and in vitro to mimic the selective neuronal degeneration that characterizes Parkinson disease (PD). To uncover candidate genes that may mediate neuron death in PD, we previously used SAGE to identify transcripts that are rapidly induced by 6-OHDA in neuronally differentiated PC12 cells. Among induced pro-apoptotic genes was that encoding the BH3-only protein PUMA. Here, we confirm that 6-OHDA induces both PUMA mRNA and protein. 6-OHDA additionally induced Bim, another pro-apoptotic BH3-only protein. Using specific siRNAs, we demonstrate that PUMA, but not Bim, is required for death evoked by 6-OHDA. PUMA is a target of p53, a transcription factor activated by 6-OHDA. Involvement of p53 in 6-OHDA evoked death was confirmed by the protective actions of a DN p53 and pifithrin alpha, inhibitors of p53 signaling. Our findings thus indicate that p53 and PUMA play required roles in a cellular model of PD.

Keywords

BH3-only neuronal apoptosis Parkinson disease PUMA 6-Hydroxydopamine 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Subhas C. Biswas
    • 1
  • Elizabeth Ryu
    • 2
    • 4
  • Clara Park
    • 3
  • Cristina Malagelada
    • 1
  • Lloyd A. Greene
    • 1
  1. 1.Department of Pathology, Center for Neurobiology and Behavior and Taub Center for Alzheimer’s Disease ResearchColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.Institute of Human NutritionColumbia University College of Physicians and SurgeonsNew YorkUSA
  3. 3.Department of Biological Sciences, College of Arts & SciencesColumbia UniversityNew YorkUSA
  4. 4.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA

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