期刊
JOURNAL OF NEUROCHEMISTRY
卷 111, 期 2, 页码 568-579出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2009.06336.x
关键词
A beta(1-42) oligomer; A beta(1-42) peptide; docosahexaenoic acid; fibrillation; SH-S5Y5 cells; toxicity
资金
- Ministry of Education, Science and Culture of Japan [19500324]
- Grants-in-Aid for Scientific Research [19500324] Funding Source: KAKEN
The mechanism of the effect of docosahexaenoic acid (DHA; C22:6, n-3), one of the essential brain nutrients, on in vitro fibrillation of amyloid beta (A beta(1-42)), A beta(1-42)-oligomers and its toxicity imparted to SH-S5Y5 cells was studied with the use of thioflavin T fluorospectroscopy, laser confocal microfluorescence, and transmission electron microscopy. The results clearly indicated that DHA inhibited A beta(1-42)-fibrill formation with a concomitant reduction in the levels of soluble A beta(1-42) oligomers. The polymerization (into fibrils) of preformed oligomers treated with DHA was inhibited, indicating that DHA not only obstructs their formation but also inhibits their transformation into fibrils. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (12.5%), Tris-Tricine gradient(4-20%) gel electrophoresis and western blot analyses revealed that DHA inhibited at least 2 species of A beta(1-42) oligomers of 15-20 kDa, indicating that it hinders these on-pathway tri/tetrameric intermediates during fibrillation. DHA also reduced the levels of dityrosine and tyrosine intrinsic fluorescence intensity, indicating DHA interrupts the microenvironment of tyrosine in the A beta(1-42) backbone. Furthermore, DHA protected the tyrosine from acrylamide collisional quenching, as indicated by decreases in Stern-Volmer constants. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide-reduction efficiency and immunohistochemical examination suggested that DHA inhibits A beta(1-42)-induced toxicity in SH-S5Y5 cells. Taken together, these data suggest that by restraining A beta(1-42) toxic tri/tetrameric oligomers, DHA may limit amyloidogenic neurodegenerative diseases, Alzheimer's disease.
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