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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Institute of Medical Sciences, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea

    Min-Kyoung Kim, Sang-Cheol Kim, Jung-Il Kang, Jae-Hee Hyun, Hye-Jin Boo, Eun-Sook Yoo & Hee-Kyoung Kang

  2. Department of Physiology, School of Medicine, Institute of Medical Sciences, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea

    Su-Yong Eun

  3. Department of Histology, School of Medicine, Institute of Medical Sciences, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea

    Deok-Bae Park

  4. Department of Neurology, School of Medicine, Institute of Medical Sciences, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea

    Ji-Hoon Kang

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  1. Min-Kyoung Kim
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Kim, MK., Kim, SC., Kang, JI. et al. 6-Hydroxydopamine-Induced PC12 Cell Death is Mediated by MEF2D Down-regulation. Neurochem Res 36, 223–231 (2011). https://doi.org/10.1007/s11064-010-0309-x

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