title: Induction of protein conformational change in mouse senile amyloidosis.
abstract: Aggregated amyloid fibrils can induce further polymerization of precursor proteins in vitro, thus providing a possible basis for propagation or transmission in the pathogenesis of amyloidoses. Previously, we postulated that the transmission of amyloid fibrils induces conformational changes of endogenous amyloid protein in mouse senile amyloidosis (Xing, Y., Nakamura, A., Chiba, T., Kogishi, K., Matsushita, T., Fu, L., Guo Z., Hosokawa, M., Mori, M., and Higuchi, K. (2001) Lab. Invest. 81, 493-499). To further characterize this transmissibility, we injected amyloid fibrils (AApoAII(C)) of amyloidogenic C type apolipoprotein A-II (APOAIIC) intravenously into 2-month-old SAMR1 mice, which have B type apolipoprotein A-II (APOAIIB), and develop few if any amyloid deposits spontaneously. 10 months after amyloid injection, deposits were detected in the tongue, stomach, intestine, lungs, heart, liver, and kidneys. The intensity of deposition increased thereafter, whereas no amyloid was detected in distilled water-injected SAMR1 mice, even after 20 months. The deposited amyloid was composed of endogenous APOAIIB with a different amyloid fibril conformation. The injection of these amyloid fibrils of APOAIIB (AApoAII(B)) induced earlier and more severe amyloidosis in SAMR1 mice than the injection of AApoAII(C) amyloid fibrils. Thus, AApoAII(C) from amyloidogenic mice could induce a conformational change of less amyloidogenic APOAIIB to a different amyloid fibril structure, which could also induce amyloidosis in the less amyloidogenic strain. These results provide important insights into the pathogenesis of amyloid diseases.
authors.affiliation: Department of Aging Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Xing
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Korenaga
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Guo
authors.forename: Junjie
authors.initials: J
authors.lastname: Yao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kogishi
authors.forename: Masanori
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D017772:Amyloid Neuropathies / Q000378:metabolism*; D000818:Animals; D016633:Apolipoprotein A-II / Q000737:chemistry*; D051379:Mice; D008854:Microscopy, Electron; D010641:Phenotype; D011487:Protein Conformation; D017510:Protein Folding; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000682:Amyloid; D016633:Apolipoprotein A-II