Protective effects of 15-deoxy-Δ12,14-prostaglandin J 2 against glutamate-induced cell death in primary cortical neuron cultures: Induction of adaptive response and enhancement of cell tolerance primarily through up-regulation of cellular glutathione

Yoshiro Saito, Keiko Nishio, Yumiko Numakawa, Yoko Ogawa, Yasukazu Yoshida, Noriko Noguchi, Etsuo Niki

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

There is increasing evidence to suggest that reactive oxygen species, including a variety of lipid oxidation products and other physiologically existing oxidative stimuli, can induce an adaptive response and enhance cell tolerance. In the present study, by using cultured cortical neurons, we investigated the effect of electrophilic lipids, such as 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxy-2-nonenal (4-HNE) against the cell death induced by H 2O2 and glutamate. Pre-treatment with both 15d-PGJ 2 and 4-HNE at sublethal concentrations resulted in a significant protective effect against oxidative stress, and 15d-PGJ2, in particular, exhibited a complete protective effect against glutamate-induced neuronal cell death. Pre-treatment with 15d-PGJ2 increased the intracellular glutathione (GSH) as well as the gene expression of glutamate-cysteine ligase (GCL), the rate-limiting enzyme of GSH synthesis. 15d-PGJ2 protected cells from glutamate-induced GSH depletion, while the inhibition of cellular GSH synthesis by buthionine sulfoximine abolished the adaptive response induced by 15d-PGJ2. These findings indicate that at low levels, 15d-PGJ2 acts as a potent survival mediator against glutamate-induced insults via the induction of an adaptive response primarily through the up-regulation of the intracellular GSH synthesis.

Original languageEnglish
Pages (from-to)1625-1634
Number of pages10
JournalJournal of Neurochemistry
Volume102
Issue number5
DOIs
Publication statusPublished - 2007 Sep
Externally publishedYes

Keywords

  • 15d-PGJ
  • Adaptive response
  • Glutamate
  • Glutathione
  • Neurotoxicity
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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