Premium
Protective effects of 15‐deoxy‐Δ 12,14 ‐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
Author(s) -
Saito Yoshiro,
Nishio Keiko,
Numakawa Yumiko,
Ogawa Yoko,
Yoshida Yasukazu,
Noguchi Noriko,
Niki Etsuo
Publication year - 2007
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.1471-4159.2007.04701.x
Subject(s) - glutathione , intracellular , glutamate receptor , buthionine sulfoximine , biology , programmed cell death , microbiology and biotechnology , oxidative stress , neuroprotection , biochemistry , cell , pharmacology , enzyme , apoptosis , receptor
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‐Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ) and 4‐hydroxy‐2‐nonenal (4‐HNE) against the cell death induced by H 2 O 2 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‐PGJ 2 , in particular, exhibited a complete protective effect against glutamate‐induced neuronal cell death. Pre‐treatment with 15d‐PGJ 2 increased the intracellular glutathione (GSH) as well as the gene expression of glutamate‐cysteine ligase (GCL), the rate‐limiting enzyme of GSH synthesis. 15d‐PGJ 2 protected cells from glutamate‐induced GSH depletion, while the inhibition of cellular GSH synthesis by buthionine sulfoximine abolished the adaptive response induced by 15d‐PGJ 2 . These findings indicate that at low levels, 15d‐PGJ 2 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.