Zamotin Vladimir, Gharibyan Anna, Gibanova Natalia V, Lavrikova Marika A, Dolgikh Dmitry A, Kirpichnikov Michail P, Kostanyan Irina A, Morozova-Roche Ludmilla A
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
FEBS Lett. 2006 May 1;580(10):2451-7. doi: 10.1016/j.febslet.2006.03.074. Epub 2006 Apr 7.
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.
原纤维前细胞毒性被认为是淀粉样蛋白的一个共同特征。我们发现，在pH 7.3孵育过程中会形成两种类型的阿尔贝西汀原纤维前寡聚体。最初的圆形寡聚体由原子力显微镜测定为包含10 - 15个分子，不与硫黄素-T结合，也不影响颗粒神经元和SH - SY5Y细胞的活力。它们会转化为约30 - 40聚体，具有交叉β-折叠结构并降低神经元细胞的活力。单体和纤维均不具有细胞毒性。我们认为寡聚体大小对于稳定对细胞毒性至关重要的交叉β-折叠核心很重要。由于阿尔贝西汀被用作药物递送的载体蛋白，在多肽生物医学应用之前需要检测其淀粉样变性。
