Neuroprotective cytokines repress PUMA induction in the 1-methyl-4-phenylpyridinium (MPP+) model of Parkinson's disease

作者：Kook Yeon Hee; Ka Minhan; Um Moonkyoung^*

来源：Biochemical and Biophysical Research Communications, 2011, 411(2): 370-374.

DOI：10.1016/j.bbrc.2011.06.151

• Parkinson's disease
• 1-Methyl-4-phenylpyridinium (MPP+)
• PUMA
• Erythropoietin
• Granulocyte-colony stimulating factor
• p53

The hematopoietic cytokines erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF) provide neuroprotection in several in vitro and in vivo models of Parkinson's disease (PD). The molecular mechanism by which Epo and G-CSF signals reduce the neuronal death in PD is not clear. Here, we show that in rat pheochromocytoma PC12 cells, Epo and G-CSF efficiently repressed the 1-methyl-4-phenylpyridinium (MPP+)-induced expression of the proapoptotic protein PUMA (p53 up-regulated modulator of apoptosis). Accordingly, Epo and G-CSF treatment reduced the PC12 cell fraction that underwent apoptosis by MPP+ treatment and thus improved cell viability. Downregulation of PUMA expression by Epo and G-CSF in MPP+-treated PC12 cells seems to be mediated by repression of p53, as the expression of p53 was increased by MPP+-treatment and reduced by Epo and G-CSF. Together, these results suggest that the neuroprotective activities of Epo and G-CSF in an experimental model of PD involve the repression of the apoptosis-inducing action of PUMA.

• 出版日期2011-7-29