Effect of Prnp gene to prion protein expression

Prnp基因对朊病毒蛋白表达的影响

• 批准号: 12460131
• 负责人: ONODERA Takashi
• 金额: $ 9.28万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12460131/
• 关键词: prion; prion protein; serapie; Cu; Zn SOD; mouse; Doppel; gene tageting; neural degeneration; Dopple; ドッペル; ノックアウトマウス; 狂牛病; 牛海綿状脳症; 遺伝子導入; 免疫組織化学

Some of the authors previously demonstrated the relation between cellular prion protein (PrP^c) and apoptosis using immortalized prion protein gene (Prnp)-deficient neuronal cells. However, the mechanism(s) by which PrP^c prevents apoptosis remains unclear. In this study, the authors analyzed apoptosis of Prnp^<-/-> cells using gene transfer of apoptosis-related genes. Transfection of Prnp^<-/-> cells with bcl-2, bcl-x_L or SOD-1, which encodes Cu/Zn superoxide dismutase (SOD), inhibited apoptosis induced by serum deprivation. As serum deprivation decreased Bcl-2 and Bcl-x_L proteins in-Prnp^<-/-> cells, these cells are thought to die via apoptosis pathways regulated by the Bcl-2 family and intracellular superoxides. Re-introduction of Prnp upregulated SOD activity and eliminated superoxide anion generation without inducing changes hi Bcl-2, Bcl-x_L and Cu/Zn SOD expression levels. As PrP^c was bound to copper in the octapeptide repeats, these results suggested that PrP^c inhibited apoptosis by upregulation of SOD activity due to copper metabolism regulation.

一些作者先前使用永生化朊蛋白基因（Prnp）缺陷的神经元细胞证明了细胞朊蛋白（PrP^c）与凋亡之间的关系。然而，PrP^c阻止细胞凋亡的机制仍不清楚。在这项研究中，作者使用凋亡相关基因的基因转移分析了Prnp^<-/->细胞的凋亡。用bcl-2、bcl-x_L或编码Cu/Zn超氧化物歧化酶（SOD）的SOD-1转染Prnp^<-/->细胞，可抑制血清剥夺诱导的细胞凋亡。由于血清剥夺降低了-Prnp ^<-/->细胞中的Bcl-2和Bcl-x_L蛋白，因此认为这些细胞通过由Bcl-2家族和细胞内超氧化物调节的凋亡途径死亡。Prnp的重新引入可上调SOD活性并消除超氧阴离子的产生，而不引起Bcl-2、Bcl-x_L和Cu/Zn SOD表达水平的变化。由于PrP^c在八肽重复序列中与铜结合，这些结果表明PrP ^c通过上调SOD活性抑制细胞凋亡，而SOD活性的上调是由于铜代谢调节所致。

项目成果

Seo S.W., Onodera T. et al.: "Comparative analysis of the prion protein ORF nucleotide sequences from the wild ruminants nufflon and golden takin"Intervirology. 44. 359-363 (2001)

Seo S.W.、Onodera T. 等人：“来自野生反刍动物纳福隆和金羚的朊病毒蛋白 ORF 核苷酸序列的比较分析”Intervirology。

Kurosaki A, Onodera T. et al.: "Developmental expression and localization of IA-2 mRNA in mouse neuroendocrine tissue"Biochem. Biophys. Res. Commun.. 288. 165-171 (2001)

Kurosaki A、Onodera T. 等：“小鼠神经内分泌组织中 IA-2 mRNA 的发育表达和定位”Biochem。

Kuwahara,c.,Onodera,T. et al.: "Enhanced expression of cellular prion protein gene by insulin or nerve growth factor."Biochemical and Biophysical Research Communications. 268. 763-766 (2000)

桑原，c.，小野寺，T.

Seo S.W., Onodera T. et al.: "Comparative analysis of the prion protein ORF nucleotide sequences from the wild ruminants mufflon and golden takin"Intervirology. 44. 359-363 (2001)

Seo S.W.、Onodera T. 等人：“来自野生反刍动物马弗隆和金羚的朊病毒蛋白 ORF 核苷酸序列的比较分析”Intervirology。

Shimizu S, Onodera T. et al.: "Developmental expression and localization of IA-2 mRNA in mouse neuroendocrine tissue"Biochem.Biophys.Res.Commun.. 288. 165-171 (2001)

Shimizu S，Onodera T.等人：“小鼠神经内分泌组织中IA-2 mRNA的发育表达和定位”Biochem.Biophys.Res.Commun..288.165-171(2001)