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Wild‐type, Flemish, and Dutch amyloid‐ β exhibit different cytotoxicities depending on A β 40 to A β 42 interaction time and concentration ratio
Author(s) -
Shahnawaz Md.,
Sharoar Md. Golam,
Shin Song Yub,
Park IlSeon
Publication year - 2013
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2531
Subject(s) - cytotoxicity , flemish , incubation , peptide , chemistry , amyloid (mycology) , cytotoxic t cell , microbiology and biotechnology , stereochemistry , biochemistry , in vitro , biology , inorganic chemistry , archaeology , history
Addition of amyloid β (A β ) peptide A β 40 to A β 42 can delay A β 42 aggregation, but consequent cytotoxicity has been reported to be enhanced or diminished. In the present study, we found that cytotoxicity was enhanced when human neuroblastoma SH‐SY5Y cells were incubated in a mixture of wt A β 42 and A β 40wt at a ratio of 1 : 10–20 (0.1 : 1–2 μM) for 24–36 h, whereas the enhancement was detected in cells incubated for longer times (48–60 h) with the less amyloidogenic Flemish A β 40 variant or in cells incubated for as short as 12 h with the more amyloidogenic Dutch variant. Reductions in cytotoxicity by A β 40 were most prominently observed in the Flemish and wt A β 40/A β 42 mixture at ratio 1 : 20 incubated for a short time (~12 h). The most cytotoxic A β 40/A β 42 mixtures were enriched in A β protofibril‐like structures, implying a strong correlation between cytotoxicity and this structure, the formation of which was dependent on amyloidogenic properties and incubation time. The consequences of the interactions were probably because of the different amyloidogenic properties of the A β 40 variants, rather than to those of A β 42, because aggregation rates of A β 40 variants were highly dependent on sequence, whereas those of A β 42 variants were not. These studies highlight a potential role for A β 40 in cytotoxicity and provide novel mechanistic insights into the pathogenesis of each familial Alzheimer's disease‐associated A β 40 variant. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.