Center for Natural Sciences and Humanities, Federal University of ABC (UFABC), Avenida dos Estados, 5001, Bl.B, Santo André, SP, 09210-580, Brazil.
Mol Cell Biochem. 2021 May;476(5):2149-2158. doi: 10.1007/s11010-021-04078-5. Epub 2021 Feb 5.
The cellular prion protein (PrP) is anchored in the plasma membrane of cells, and it is highly present in cells of brain tissue, exerting numerous cellular and cognitive functions. The present study proves the importance of PrP in the cellular defense mechanism and metal homeostasis in astrocytes cells. Through experimental studies using cell lines of immortalized mice astrocytes (wild type and knockout for PrP), we showed that PrPc is involved in the apoptosis cell death process by the activation of Caspase 3, downregulation of p53, and cell cycle maintenance. Metal homeostasis was determined by inductively coupled plasma mass spectrometry technique, indicating the crucial role of PrP to lower intracellular calcium. The lowered calcium concentration and the Caspase 3 downregulation in the PrP-null astrocytes resulted in a faster growth rate in cells, comparing with PrP wild-type one. The presence of PrP shows to be essential to cell death and healthy growth. In conclusion, our results show for the first time that astrocyte knockout cells for the cellular prion protein could modulate apoptosis-dependent cell death pathways.
细胞朊蛋白（PrP）锚定在细胞膜上，在脑组织细胞中高度存在，发挥多种细胞和认知功能。本研究证明了 PrP 在星形胶质细胞的细胞防御机制和金属动态平衡中的重要性。通过使用永生化小鼠星形胶质细胞系（野生型和 PrP 敲除型）的实验研究，我们表明 PrPc 通过激活 Caspase 3、下调 p53 和细胞周期维持参与细胞凋亡过程。通过电感耦合等离子体质谱技术测定金属动态平衡，表明 PrP 在降低细胞内钙方面起着关键作用。PrP 缺失的星形胶质细胞中钙浓度降低和 Caspase 3 下调导致细胞生长速度加快，与 PrP 野生型相比。PrP 的存在对于细胞死亡和健康生长是必不可少的。总之，我们的结果首次表明，星形胶质细胞中细胞朊蛋白的缺失可调节依赖凋亡的细胞死亡途径。
