Chonbuk National University, Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Jeonju, Jeonbuk 561-756, South Korea.
Biochem Biophys Res Commun. 2010 Oct 29;401(4):516-20. doi: 10.1016/j.bbrc.2010.09.078. Epub 2010 Sep 25.
The prion diseases are neurodegenerative disorders characterized by the conversion of the PrPc (normal cellular prion) to the PrPsc (misfolded isoform). The accumulation of PrPsc within the central nervous system (CNS) leads to neurocytotoxicity by increasing oxidative stress. In addition, many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be regulated by cholesterol homeostasis. The effects of cholesterol balance on prion protein-mediated neurotoxicity and ROS (reactive oxygen species) generation were the focus of this study. Cholesterol treatment inhibited PrP (106-126)-induced neuronal cell death and ROS generation in SH-SY5Y neuroblastoma cells. In addition, the PrP (106-126)-mediated increase of p53, p-p38, p-ERK and the decrease of Bcl-2 were blocked by cholesterol treatment. These results indicated that cellular cholesterol enrichment is a key regulator of PrP-106-126-mediated oxidative stress and neurotoxicity. Taken together, the results of this study suggest that modulation of cellular cholesterol appears to prevent the neuronal cell death caused by prion peptides.
朊病毒病是一种神经退行性疾病，其特征是 PrPc（正常细胞朊病毒）转化为 PrPsc（错误折叠的异构体）。PrPsc 在中枢神经系统（CNS）中的积累通过增加氧化应激导致神经毒性。此外，包括朊病毒、帕金森病和阿尔茨海默病在内的许多神经退行性疾病可能受胆固醇稳态调节。本研究的重点是胆固醇平衡对朊病毒蛋白介导的神经毒性和 ROS（活性氧）生成的影响。胆固醇处理抑制了 SH-SY5Y 神经母细胞瘤细胞中 PrP（106-126）诱导的神经元细胞死亡和 ROS 生成。此外，胆固醇处理阻断了 PrP（106-126）介导的 p53、p-p38、p-ERK 的增加和 Bcl-2 的减少。这些结果表明，细胞胆固醇的富集是 PrP-106-126 介导的氧化应激和神经毒性的关键调节剂。总之，本研究结果表明，细胞胆固醇的调节似乎可以防止朊病毒肽引起的神经元细胞死亡。
