Abstract Title:

Mechanism of docosahexaenoic acid-induced inhibition of in vitro Abeta1-42 fibrillation and Abeta1-42-induced toxicity in SH-S5Y5 cells.

Abstract Source:

J Neurochem. 2009 Oct;111(2):568-79. Epub 2009 Aug 17. PMID: 19686246

Abstract Author(s):

Shahdat Hossain, Michio Hashimoto, Masanori Katakura, Koji Miwa, Toshio Shimada, Osamu Shido

Abstract:

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 (Abeta(1-42)), Abeta(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 Abeta(1-42)-fibrill formation with a concomitant reduction in the levels of soluble Abeta(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 Abeta(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 Abeta(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 Abeta(1-42)-induced toxicity in SH-S5Y5 cells. Taken together, these data suggest that by restraining Abeta(1-42) toxic tri/tetrameric oligomers, DHA may limit amyloidogenic neurodegenerative diseases, Alzheimer's disease.

Study Type : In Vitro Study

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