Waqas Muhammad, Lee Hye-Mi, Kim Jeeyoung, Telling Glenn, Kim Jin-Ki, Kim Dae-Hwan, Ryou Chongsuk
Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Mol Cell Biochem. 2017 Apr;428(1-2):57-66. doi: 10.1007/s11010-016-2916-6. Epub 2017 Jan 7.
Biological effect of poly-L-arginine (PLR), the linear homopolymer comprised of L-arginine, was investigated to determine the activity of suppressing prions. PLR decreased the level of scrapie prion protein (PrP) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrP inhibition efficacy of PLR was greater than that of another prion-suppressant poly-L-lysine (PLK) in a molecular mass-dependent fashion. The effective concentration of PLR to inhibit prions was achieved safely below the cytotoxic concentrations, and overall cytotoxicity of PLR was similar to that of PLK. PLR did not alter the cellular prion protein (PrP) level and was unable to change the states of preformed recombinant PrP aggregates and PrP from prion-infected cells. These data eliminate the possibility that the action mechanism of PLR is through removal of PrP and pre-existing PrP. However, PLR formed complexes with plasminogen that stimulates prion propagation via conversion of PrP to the misfolded isoform, PrP. The plasminogen-PLR complex demonstrated the greater positive surface charge values than the similar complex with PLK, raising the possibility that PLR interferes with the role of cofactor for PrP generation better than PLK.
研究了由L-精氨酸组成的线性均聚物聚-L-精氨酸（PLR）的生物学效应，以确定其抑制朊病毒的活性。PLR以浓度依赖性方式降低了被朊病毒持续感染的培养细胞中瘙痒病朊病毒蛋白（PrP）的水平。PLR对PrP的抑制效果在分子量依赖性方面大于另一种朊病毒抑制剂聚-L-赖氨酸（PLK）。在细胞毒性浓度以下安全地达到了PLR抑制朊病毒的有效浓度，并且PLR的总体细胞毒性与PLK相似。PLR没有改变细胞朊病毒蛋白（PrP）水平，并且无法改变预先形成的重组PrP聚集体和来自朊病毒感染细胞的PrP的状态。这些数据排除了PLR的作用机制是通过去除PrP和预先存在的PrP的可能性。然而，PLR与纤溶酶原形成复合物，纤溶酶原通过将PrP转化为错误折叠的异构体PrP来刺激朊病毒繁殖。纤溶酶原-PLR复合物显示出比与PLK的类似复合物更大的正表面电荷值，这增加了PLR比PLK更好地干扰PrP产生辅因子作用的可能性。
