Cytotoxicity of albebetin oligomers depends on cross-beta-sheet formation.
Prefibrillar cytotoxicity was suggested as a common amyloid characteristic. We showed two types of albebetin prefibrillar oligomers are formed during incubation at pH 7.3. Initial round-shaped oligomers consist of 10-15 molecules determined by atomic force microscopy, do not bind thioflavin-T and do not affect viability of granular neurons and SH-SY5Y cells. They are converted into ca. 30-40-mers possessing cross-beta-sheet and reducing viability of neuronal cells. Neither monomers nor fibrils possess cytotoxicity. We suggest that oligomeric size is important for stabilising cross-beta-sheet core critical for cytotoxicity. As albebetin was used as a carrier-protein for drug delivery, examination of amyloidogenicity is required prior polypeptide biomedical applications.
Zamotin
Vladimir
V
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
Gharibyan
Anna
A
Gibanova
Natalia V
NV
Lavrikova
Marika A
MA
Dolgikh
Dmitry A
DA
Kirpichnikov
Michail P
MP
Kostanyan
Irina A
IA
Morozova-Roche
Ludmilla A
LA
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001704:Biopolymers / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002942:Circular Dichroism; D008297:Male; D018625:Microscopy, Atomic Force; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000633:toxicity; D013056:Spectrophotometry, Ultraviolet
D000682:Amyloid; D001704:Biopolymers; D011506:Proteins; D011994:Recombinant Proteins; C074146:albebetin