Propofol protection of sodium-hydrogen exchange activity sustains glutamate uptake during oxidative stress
Propofol protection of sodium-hydrogen exchange activity sustains glutamate uptake during oxidative stress
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DOI：
10.1097/00000539-200111000-00030
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发表时间：
2001-11-01
影响因子：
5.7
通讯作者：
Wilson, JX
中科院分区：
文献类型：
--
作者：
Daskalopoulos, R;Korcok, J;Wilson, JX
我们研究了氧化应激过程中细胞内 pH 值在异丙酚保护谷氨酸吸收中的作用。将原代星形胶质细胞培养物暴露于叔丁基过氧化氢（t-BOOH，300 muM）会降低Na依赖性谷氨酸吸收的初始速率。 t-BOOH 后 30 分钟施用异丙酚或 α-生育酚，可减弱这种转运抑制。这些亲脂性抗氧化剂。无论培养基含有 25 mM 碳酸氢盐还是名义上不含碳酸氢盐，都能保护谷氨酸的吸收。 t-BOOH 还抑制 Na/H 交换异构体。 I (NHE1) 被细胞内质子和异丙酚激活可阻止这种抑制。通过强效拮抗剂 5-(N-乙基-N-异丙基)阿米洛利 (1 μM) 阻断 NHE1，消除了小浓度丙泊酚 (1 μM) 和 α-生育酚 (40 μM) 对无碳酸氢盐培养基中氧化应激期间谷氨酸摄取的保护作用。 5-(N乙基-N-异丙基)阿米洛利对含有 25 mM 碳酸氢盐的培养基中谷氨酸转运的抗氧化救援没有影响。这些结果表明，细胞内 pH 值的调节可能有助于丙泊酚和其他亲脂性抗氧化剂的神经保护作用。与麻醉和神经保护相关的异丙酚浓度可以通过保留 NHE1 对胞质质子的反应来防止氧化应激期间的细胞内酸化。然而，如果细胞内酸化仍然发生，那么异丙酚对谷氨酸摄取活性的保护作用就会变得不那么有效，并且细胞外谷氨酸浓度可能会增加到神经毒性水平。
We investigated the role of intracellular pH in protection by propofol of glutamate uptake during oxidative stress. Exposure of primary astrocyte cultures to tert-butylhydroperoxide (t-BOOH, 300 muM) decreased the initial rate of Na-dependent glutamate uptake. Either propofol or alpha -tocopherol, administered 30 min after t-BOOH, attenuated this transport inhibition. These lipophilic antioxidants. protected glutamate uptake whether the medium contained 25 mM bicarbonate or was nominally bicarbonate-free. t-BOOH also inhibited Na/H exchanger isoform. I (NHE1) activation by intracellular protons and propofol prevented this inhibition. Blockade of NHE1 by the potent antagonist, 5-(N-ethyl-N-isopropyl) amiloride (I muM), abolished the protective effects of small concentrations of propofol (1 muM) and a-tocopherol (40 muM) on glutamate uptake during oxidative stress in bicarbonate-free medium. 5-(Nethyl-N-isopropyl) amiloride had no effect on antioxidant rescue of glutamate transport in medium containing 25 mM bicarbonate. These results indicate that regulation of intracellular pH may contribute to neuroprotection by propofol and other lipophilic antioxidants. Propofol concentrations that are associated with anesthesia and neuroprotection may prevent intracellular acidification during oxidative stress by preserving the NHE1 response to cytosolic protons. However, if intracellular acidification occurs nonetheless, then propofol protection of glutamate uptake activity becomes less effective and the extracellular glutamate concentration may increase to neurotoxic levels.