Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.
Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.
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DOI：
10.1097/aln.0b013e3182833fae
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发表时间：
2013-03
期刊：
影响因子：
8.8
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Zhao X;Yang Z;Liang G;Wu Z;Peng Y;Joseph DJ;Inan S;Wei H
先前的研究表明，异氟烷可以在各种组织培养模型和啮齿动物发育中的大脑中提供神经保护和神经毒性。介导这些双重作用的细胞和分子机制尚不清楚，但异氟烷的暴露水平和持续时间似乎是决定因素。使用 ReNcell CX 人类神经祖细胞系，我们研究了长期暴露于不同异氟烷浓度对细胞存活和神经发生的影响。此外，我们评估了短时间异氟烷预处理对胞质 Ca2+ 浓度升高的影响和长时间异氟烷暴露介导的细胞毒性作用，以及 InsP3 或兰尼定受体激活对这些过程的贡献。短时间暴露于低浓度异氟烷可促进 ReNcell CX 细胞的增殖和分化，且不会造成细胞损伤。然而，长时间暴露于高浓度异氟醚会导致 ReNcell CX 细胞显着损伤并抑制细胞增殖。这些长时间的暴露抑制了神经元细胞的命运，同时促进了神经胶质细胞的命运。对 ReNcell CX 培养物进行短时间暴露于低浓度异氟烷的预处理可改善长期暴露于异氟烷的影响。用 InsP3 或兰尼定受体拮抗剂对 ReNcell 培养物进行预处理，大部分可以防止异氟烷介导的对存活、增殖和分化的影响。最后，异氟烷预处理的培养物显示异氟烷引起的钙浓度变化明显较小。常用的全身麻醉剂异氟烷对神经元干细胞的存活、增殖和分化产生双重影响，这可能是由于通过激活内质网局部的 InsP3 和/或兰尼碱受体对钙释放的差异调节。
Previous studies have demonstrated that isoflurane can provide both neuroprotection and neurotoxicity in various tissue culture models and in rodent developing brains. The cellular and molecular mechanisms mediating these dual effects are not clear, but the exposure level and duration of isoflurane appear to be determinant factors. Using the ReNcell CX human neural progenitor cell line, we investigated the impact of prolonged exposure to varying isoflurane concentrations on cell survival and neurogenesis. In addition, we assessed the impact of short isoflurane preconditioning on elevation of cytosolic Ca2+ concentration and cytotoxic effects mediated by prolonged isoflurane exposures and the contribution of InsP3 or ryanodine receptors activation to these processes. Short exposures to low isoflurane concentrations promote proliferation and differentiation of ReNcell CX cells, with no cell damage. However, prolonged exposures to high isoflurane concentrations induced significant ReNcell CX cell damage and inhibited cell proliferation. These prolonged exposures suppressed neuronal cell fate, while promoting glial cell fate. Preconditioning of ReNcell CX cultures with short exposures to low concentrations of isoflurane ameliorated the effects of prolonged exposures to isoflurane. Pretreatment of ReNcell cultures with InsP3 or ryanodine receptor antagonists mostly prevented isoflurane-mediated effects on survival, proliferation, and differentiation. Finally, isoflurane preconditioned cultures showed significantly less isoflurane-evoked changes in calcium concentration. The commonly used general anesthetic isoflurane exerts dual effects on neuronal stem cell survival, proliferation and differentiation, which may be attributed to differential regulation of calcium release through activation of endoplasmic reticulum localized InsP3 and/or ryanodine receptors.