Protective effects of 15‐deoxy‐Δ12,14‐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
Protective effects of 15‐deoxy‐Δ12,14‐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
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DOI：
10.1111/j.1471-4159.2007.04701.x
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发表时间：
2007-09
影响因子：
4.7
通讯作者：
Yoshiro Saito;K. Nishio;Yumiko Numakawa;Yoko Ogawa;Y. Yoshida;N. Noguchi;E. Niki
中科院分区：
文献类型：
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作者：
Yoshiro Saito;K. Nishio;Yumiko Numakawa;Yoko Ogawa;Y. Yoshida;N. Noguchi;E. Niki
越来越多的证据表明，活性氧，包括各种脂质氧化产物和其他生理上存在的氧化刺激，可以诱导适应性反应，增强细胞耐受性。在本研究中，我们使用培养的皮层神经元，研究亲电脂质，如15-脱氧-Δ 12，14-前列腺素J2（15 d-PGJ 2）和4-羟基-2-壬烯醛（4-HNE）对H2 O2和谷氨酸诱导的细胞死亡的影响。用亚致死浓度的15 d-PGJ 2和4-HNE预处理导致对氧化应激的显著保护作用，特别是15 d-PGJ 2对谷氨酸诱导的神经元细胞死亡表现出完全的保护作用。用15 d-PGJ 2预处理增加了细胞内谷胱甘肽（GSH）以及谷氨酸-半胱氨酸连接酶（GCL）（GSH合成的限速酶）的基因表达。15 d-PGJ 2保护细胞免受谷氨酸诱导的GSH耗竭，而丁硫基乙砜亚胺抑制细胞GSH合成则消除了15 d-PGJ 2诱导的适应性反应。这些发现表明，在低水平下，15 d-PGJ 2通过主要通过上调细胞内GSH合成诱导适应性反应，作为对抗谷氨酸诱导的损伤的有效存活介质。
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 H2O2 and glutamate. Pre‐treatment with both 15d‐PGJ2 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.