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Neurochemical Research

, Volume 36, Issue 2, pp 223–231 | Cite as

6-Hydroxydopamine-Induced PC12 Cell Death is Mediated by MEF2D Down-regulation

  • Min-Kyoung Kim
  • Sang-Cheol Kim
  • Jung-Il Kang
  • Jae-Hee Hyun
  • Hye-Jin Boo
  • Su-Yong Eun
  • Deok-Bae Park
  • Eun-Sook Yoo
  • Hee-Kyoung Kang
  • Ji-Hoon Kang
ORIGINAL PAPER

Abstract

Recently, it was reported that in a 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model, neuronal cell death is associated with the cdk5-mediated hyperphosphorylation of myocyte enhancer factor 2 (MEF2), a transcription factor that is critically required for neuronal survival. In the present study, we investigated the possible involvement of cdk5-mediated MEF2D down-regulation on 6-hydroxydopamine (6-OHDA)-induced PC12 cell death. 6-OHDA was found to significantly increase nitric oxide (NO) production and to induce apoptosis in a time-dependent manner in PC12 cells. Furthermore, 6-OHDA was found to markedly reduce MEF2D levels under conditions that could induce PC12 cell apoptosis. In addition, PC12 cell death and MEF2D degradation by 6-OHDA were prevented by the cdk5 inhibitor roscovitine, but roscovitine could not restore the 6-OHDA-induced inactivation of Akt. These results suggest that the cell death and MEF2D degradation caused by 6-OHDA are dependent on cdk5 activity. On the other hand, roscovitine enhanced the 6-OHDA-induced activations of ERK1/2 and JNK, but reduced the 6-OHDA-induced activation of p38. These results suggest that PC12 cell death by 6-OHDA appears to be regulated by the down-regulation of MEF2D via some interaction between cdk5 and MAP kinase.

Keywords

6-OHDA PC12 cells NO MEF2D cdk5 MAP kinase 

Notes

Acknowledgments

This work was supported by a research grant from Jeju National University in 2007.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Min-Kyoung Kim
    • 1
  • Sang-Cheol Kim
    • 1
  • Jung-Il Kang
    • 1
  • Jae-Hee Hyun
    • 1
  • Hye-Jin Boo
    • 1
  • Su-Yong Eun
    • 2
  • Deok-Bae Park
    • 3
  • Eun-Sook Yoo
    • 1
  • Hee-Kyoung Kang
    • 1
  • Ji-Hoon Kang
    • 4
  1. 1.Department of Pharmacology, School of Medicine, Institute of Medical SciencesJeju National UniversityJejuSouth Korea
  2. 2.Department of Physiology, School of Medicine, Institute of Medical SciencesJeju National UniversityJejuSouth Korea
  3. 3.Department of Histology, School of Medicine, Institute of Medical SciencesJeju National UniversityJejuSouth Korea
  4. 4.Department of Neurology, School of Medicine, Institute of Medical SciencesJeju National UniversityJejuSouth Korea

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