Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells
Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells
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DOI：
10.1023/a:1022437000893
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发表时间：
1998-01-01
影响因子：
4.4
通讯作者：
Liu, LZ
中科院分区：
文献类型：
--
作者：
Chang, JY;Phelan, KD;Liu, LZ
用神经生长因子诱导分化的PC12细胞研究25-OH-胆固醇的神经毒性。该试剂在神经元PC12细胞中诱导剂量和时间依赖性细胞死亡。用该试剂处理的细胞显示浓缩的细胞核，其形态类似于死于程序性细胞死亡的细胞。然而，已知可预防神经元程序性细胞死亡的药物（环AMP、KCl、金精三羧酸和放线菌酮）未能预防25-OH-胆固醇介导的细胞毒性。另一方面，用维生素E和甲基-β-环糊精处理可防止25-OH-胆固醇诱导的细胞死亡。与其他细胞类型的观察结果相反，神经元PC12细胞的全细胞膜片钳记录显示，用25-OH-胆固醇治疗并没有显着改变通过电压依赖性通道的钙内流。这些结果提供了第一个表征的胆固醇氧化物对神经元PC12细胞的毒性，这应该是有用的，在未来的研究胆固醇氧化物和神经系统细胞之间的相互作用。
PC12 cells induced to differentiate with nerve growth factor were used to study the neurotoxicity of 25-OH-cholesterol. This agent induced a dose-and rime-dependent cell death in neuronal PC12 cells. Cells treated with this agent showed condensed nuclei, a morphology similar to that of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarboxylic acid, and cycloheximide) failed to prevent the 25-OH-cholesterol-mediated cytotoxicity. On the other hand, cell death induced by 25-OH-cholesterol was prevented by treatment with vitamin E and methyl-beta-cyclodextrin. In contrast to observations made in other cell types, whole-cell patch clamp recording of neuronal PC12 cells revealed that treatment with 25-OH-cholesterol did not significantly alter calcium influx through voltage-dependent channels. These results provide the first characterization of the toxicity of cholesterol oxides toward neuronal PC12 cells, which should be useful in future studies on the interactions between cholesterol oxides and cells from the nervous system.