title: Protective effects of 15-deoxy-Delta12,14-prostaglandin J2 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.
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-Delta(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.
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Yoshiro
authors: Y
authors: Saito
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Keiko
authors: K
authors: Nishio
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Yumiko
authors: Y
authors: Numakawa
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Yoko
authors: Y
authors: Ogawa
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Yasukazu
authors: Y
authors: Yoshida
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Noriko
authors: N
authors: Noguchi
authors: Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, JapanLaboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, JapanDepartment of Environmental Systems Science, Faculty of Engineering, Doshisha University, Kyoto, Japan.
authors: Etsuo
authors: E
authors: Niki
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D018698:Glutamic Acid; D019328:Buthionine Sulfoximine; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D015230:Prostaglandin D2