PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42.

Boutaud O, Montine TJ, Chang L, Klein WL, Oates JA
J Neurochem. 2006 96 (4): 917-23

PMID: 16412101 · PMCID: PMC1621054 · DOI:10.1111/j.1471-4159.2005.03586.x

The body of evidence indicating that oligomers of amyloid beta(1-42) (Abeta(1-42)) produce toxicity to neurons, together with our demonstration that prostaglandin H(2) (PGH(2)) oligomerizes amyloid beta(1-42), led to the examination of the neurotoxicity of amyloid beta(1-42) treated with PGH(2). The neurotoxic effects of Abeta(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 Abeta(1-42) itself, incubated for 24 h, has little or no effect on MTT reduction, Abeta(1-42) 24 h after exposure to PGH(2) produced a marked inhibition of MTT reduction, comparable with the inhibition resulting from Abeta(1-42) that has been oligomerized by incubation for 6 days. Similar results were obtained when Abeta(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 Abeta(1-42) with LGE(2) exhibit immunochemical similarity with amyloid-derived diffusible ligands (ADDLs), as determined by analysis of the products of reaction of Abeta(1-42) with LGE(2) using western blotting with an antibody that is selective for ADDLs.

MeSH Terms (13)

Amyloid beta-Peptides Animals Cells, Cultured Cerebral Cortex Female Mice Mice, Inbred C57BL Neurons Neurotoxins Peptide Fragments Pregnancy Prostaglandin H2 Prostaglandins E

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