Effect of poly-L-arginine in inhibiting scrapie prion protein of cultured cells

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^Sc) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrP^Sc 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^C) level and was unable to change the states of preformed recombinant PrP aggregates and PrP^Sc from prion-infected cells. These data eliminate the possibility that the action mechanism of PLR is through removal of PrP^C and pre-existing PrP^Sc. However, PLR formed complexes with plasminogen that stimulates prion propagation via conversion of PrP^C to the misfolded isoform, PrP^Sc. 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^Sc generation better than PLK.