Transmissibility of mouse AApoAII amyloid fibrils: inactivation by physical and chemical methods.
AApoAII amyloid fibrils have exhibited prion-like transmissibility in mouse senile amyloidosis. We have demonstrated that AApoAII is extremely active and can induce amyloidosis following doses less than 1 pg. We tested physical and chemical methods to disrupt AApoAII fibrils in vitro as determined by thioflavin T binding and electron microscopy (EM) as well as inactivating the transmissibility of AApoAII fibrils in vivo. Complete disruption of AApoAII fibrils was achieved by treatment with formic acid, 6 M guanidine hydrochloride, and autoclaving in an alkaline solution. Injection of these disrupted AApoAII fibrils did not induce amyloidosis in mice. Disaggregation with 6 M urea, autoclaving, and alkaline solution was incomplete, and injection of these AApoAII fibrils induced mild amyloidosis. Treatment with formalin, delipidation, freeze-thaw, and RNase did not have any major effect. A distinct correlation was obtained between the amounts of amyloid fibrils and the transmissibility of amyloid fibrils, thereby indicating the essential role of fibril conformation for transmission of amyloidosis. We also studied the inactivation of AApoAII fibrils by several organic compounds in vitro and in vivo. AApoAII amyloidosis provides a valuable system for studying factors that may prevent transmission of amyloid disease as well as potential novel therapies.
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
Huanyu
H
Zhang
Jinko
J
Sawashita
Xiaoying
X
Fu
Tatsumi
T
Korenaga
Jingmin
J
Yan
Masayuki
M
Mori
Keiichi
K
Higuchi
D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D016633:Apolipoprotein A-II / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D005561:Formates / Q000494:pharmacology; D019791:Guanidine / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D011489:Protein Denaturation / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects
D000682:Amyloid; D016633:Apolipoprotein A-II; D005561:Formates; C030544:formic acid; D019791:Guanidine