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PGH 2 ‐derived levuglandin adducts increase the neurotoxicity of amyloid β1–42
Author(s) -
Boutaud Olivier,
Montine Thomas J.,
Chang Lei,
Klein William L.,
Oates John A.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03586.x
Subject(s) - neurotoxicity , chemistry , bromide , toxicity , incubation , amyloid (mycology) , microbiology and biotechnology , biochemistry , mtt assay , cell , biology , organic chemistry , inorganic chemistry
The body of evidence indicating that oligomers of amyloid β 1−42 (Aβ 1−42 ) produce toxicity to neurons, together with our demonstration that prostaglandin H 2 (PGH 2 ) oligomerizes amyloid β 1−42 , led to the examination of the neurotoxicity of amyloid β 1−42 treated with PGH 2 . The neurotoxic effects of Aβ 1−42 incubated with PGH 2 was examined in primary cultures of cerebral neurons of mice, monitoring the reduction of 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) as an indicator of cell toxicity. Whereas Aβ 1−42 itself, incubated for 24 h, has little or no effect on MTT reduction, Aβ 1−42 24 h after exposure to PGH 2 produced a marked inhibition of MTT reduction, comparable with the inhibition resulting from Aβ 1−42 that has been oligomerized by incubation for 6 days. Similar results were obtained when Aβ 1−42 was incubated with levuglandin E 2 (LGE 2 ), a reactive aldehyde formed by spontaneous rearrangement of PGH 2 . The oligomers formed from reaction of Aβ 1−42 with LGE 2 exhibit immunochemical similarity with amyloid‐derived diffusible ligands (ADDLs), as determined by analysis of the products of reaction of Aβ 1−42 with LGE 2 using western blotting with an antibody that is selective for ADDLs.