Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells / 神经科学通报·英文版

ABSTRACT

<p><b>OBJECTIVE</b>The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated.</p><p><b>METHODS</b>PC12 cells impaired by MPP(+) were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC12 cells. The expression of Bcl-2 and Bax in PC12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer.</p><p><b>RESULTS</b>Treatment of PC12 cells with MPP(+) caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP(+) significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL.</p><p><b>CONCLUSION</b>The inhibitive effect of EPO on the MPP(+)-induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.</p>