Brown D R, Schmidt B, Kretzschmar H A
Institut für Neuropathologie, Biochemie II, Universität Göttingen, Germany.
J Neurochem. 1998 Apr;70(4):1686-93. doi: 10.1046/j.1471-4159.1998.70041686.x.
The N-terminal region of the prion protein (PrP) contains an octameric repeat region suggested to bind copper. A 32-amino acid peptide (PrPOcta) based on this region in the protein was tested for its effects on cultured cerebellar cells. Cerebellar cells from mice deficient in cellular PrP (Prnp0/0 mice) are more sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes the survival of Prnp0/0 cerebellar cells. However, PrPOcta also reduces the toxicity of CuSO4 on cerebellar cells and abolishes the difference in increased sensitivity of Prnp0/0 cells to both copper toxicity and also oxidative stress from xanthine oxidase. PrPOcta does not promote the survival or proliferation of astrocytes or microglia. The survival-promoting effects of PrPOcta on neurons may be due to its ability to effectively chelate copper. The octameric repeat region of PrP may represent a functional domain of the native protein.
朊病毒蛋白（PrP）的N端区域包含一个推测可结合铜的八聚体重复区域。基于该区域的一段32个氨基酸的肽（PrPOcta），对其在培养的小脑细胞中的作用进行了测试。细胞型PrP缺陷小鼠（Prnp0/0小鼠）的小脑细胞对铜毒性和氧化应激更为敏感。PrPOcta可选择性地促进Prnp0/0小脑细胞的存活。然而，PrPOcta也可降低硫酸铜对小脑细胞的毒性，并消除Prnp0/0细胞对铜毒性和黄嘌呤氧化酶氧化应激敏感性增加的差异。PrPOcta不会促进星形胶质细胞或小胶质细胞的存活或增殖。PrPOcta对神经元的存活促进作用可能归因于其有效螯合铜的能力。PrP的八聚体重复区域可能代表天然蛋白的一个功能域。
