title: Neuroprotective cytokines repress PUMA induction in the 1-methyl-4-phenylpyridinium (MPP(+)) model of Parkinson's disease.
abstract: 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.
authors: Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.
authors: Yeon-Hee
authors: YH
authors: Kook
authors: Minhan
authors: M
authors: Ka
authors: Moonkyoung
authors: M
authors: Um
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D016159:Tumor Suppressor Protein p53
chemical_list: D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; D016207:Cytokines; D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D015655:1-Methyl-4-phenylpyridinium