title: Effect of poly-L-arginine in inhibiting scrapie prion protein of cultured cells.
abstract: 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 (PrPSc) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrPScinhibition 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 (PrPC) level and was unable to change the states of preformed recombinant PrP aggregates and PrPScfrom prion-infected cells. These data eliminate the possibility that the action mechanism of PLR is through removal of PrPCand pre-existing PrPSc. However, PLR formed complexes with plasminogen that stimulates prion propagation via conversion of PrPCto the misfolded isoform, PrPSc. 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 PrPScgeneration better than PLK.
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Waqas
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Jeeyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Telling
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea.
authors.forename: Dae-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, Republic of Korea. cryou2@hanyang.ac.kr.
authors.forename: Chongsuk
authors.initials: C
authors.lastname: Ryou
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism*; D011107:Polylysine / Q000494:pharmacology; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D010455:Peptides; D018621:PrPC Proteins; D018620:PrPSc Proteins; D020033:Protein Isoforms; D011107:Polylysine; C015462:polyarginine; D010958:Plasminogen
keywords: Inhibition; Poly-L-arginine; PrPC; PrPSc; Prion