PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid β1-42

Olivier Boutaud*, Thomas J. Montine, Lei Chang, William L. Klein, John A. Oates

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The body of evidence indicating that oligomers of amyloid β1-42 (Aβ1-42) produce toxicity to neurons, together with our demonstration that prostaglandin H2 (PGH 2) oligomerizes amyloid β1-42, led to the examination of the neurotoxicity of amyloid β1-42 treated with PGH 2. The neurotoxic effects of Aβ1-42 incubated with PGH2 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 Aβ1-42 itself, incubated for 24 h, has little or no effect on MTT reduction, Aβ1-42 24 h after exposure to PGH2 produced a marked inhibition of MTT reduction, comparable with the q6inhibition resulting from Aβ1-42 that has been oligomerized by incubation for 6 days. Similar results were obtained when Aβ1-42 was incubated with levuglandin E2 (LGE2), a reactive aldehyde formed by spontaneous rearrangement of PGH2. The oligomers formed from reaction of Aβ1-42 with LGE2 exhibit immunochemical similarity with amyloid-derived diffusible ligands (ADDLs), as determined by analysis of the products of reaction of Aβ1-42 with LGE2 using western blotting with an antibody that is selective for ADDLs.

Original languageEnglish (US)
Pages (from-to)917-923
Number of pages7
JournalJournal of neurochemistry
Volume96
Issue number4
DOIs
StatePublished - Feb 2006

Keywords

  • Amyloid
  • Amyloid-derived diffusible ligands
  • Cyclooxygenase
  • Levuglandin
  • Neurotoxicity
  • Prostaglandin H.

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'PGH<sub>2</sub>-derived levuglandin adducts increase the neurotoxicity of amyloid β1-42'. Together they form a unique fingerprint.

Cite this