Neurotoxic Effect of the Complex of the Ovine Prion Protein (OvPrPC) and RNA on the Cultured Rat Cortical Neurons
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Prion diseases are conformational diseases, many factors are involved in altering the conformation of prion, such as RNA, DNA, pH, and copper etc. However the neurotoxic mechanism of prion diseases is not clear yet. The aim of this study is to investigate the effect of the nucleoprotein complex of RNA and recombinant ovine prion protein (OvPrPC) on the cultured rat cortical neurons in vitro. Our previous study revealed that the nucleoprotein complex (OvPrPC-RNA) is characterized with high β sheet conformation and proteinase K resistance. Here we found that the OvPrPC-RNA induced marked neuronal cell death by the MTT (3-(4,5-dimethyl-thiazole -2-yl)-2,5-diphenyl –tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and the neurotoxic effects were confirmed by testing the content of Bcl-2 Associated X protein (Bax) in the immunoprecipitation assay and Western blot assay. Compared to the control group, there is no significant difference of active Bax or total Bax after RNA alone treatment or OvPrPC alone treatment, but the OvPrPC-RNA induced significant increases of active Bax level, while the contents of total Bax had no obvious changes after OvPrPC-RNA treatment. The results suggested that OvPrPC-RNA is neurotoxic in vitro, which added further evidence to the current understanding of mechanism of cellular injury by RNA molecules for transformation of the PrPC to PrPSc.
KeywordsPrion OvPrPC-RNA Neuronal injury neurotoxicity Bax
This work was supported by the NSFC (No. 30871854), NSFC Research Grant (10925208) and by Research Fund for the Doctoral Program of Higher Education of China (20091102110031) and also supported by the Fundamental Research Funds for the Central Universities (YWF-11-03-Q-056).
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