Neurotoxicity of 25-OH-cholesterol on sympathetic neurons
Neurotoxicity of 25-OH-cholesterol on sympathetic neurons
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DOI：
10.1016/s0361-9230(97)00461-9
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发表时间：
1998-04-01
影响因子：
3.8
通讯作者：
Chavis, JA
中科院分区：
文献类型：
--
作者：
Chang, JY;Phelan, KD;Chavis, JA
采用体外培养的大鼠上级颈神经节（SCG）交感神经元，比较了几种胆固醇氧化物的神经毒性。检测的胆固醇氧化物包括：7-β-OH-、7-酮-、19-OH-、22（R）-OH-、22（S）-OH-和25-OH-胆固醇。这些药物引起了急性和延迟毒性交感神经元与PB-OH-胆固醇似乎是最有毒的。时间依赖性实验表明，4 μ g/ml（10 μ M）的PB-OH-胆固醇能够在36小时内杀死50%的细胞。形态学研究表明，大多数细胞没有表现出类似于在神经元程序性细胞死亡中观察到的结构变化。未处理对照和2B-OH-胆固醇（2 μ g/ml）处理细胞的全细胞膜片钳记录表明，这种毒性不伴随电压依赖性钙通道活性的显著变化。包括乙二醇双（β-氨基乙基醚）N，N，N '，N'-四乙酸（EGTA）、放线菌酮、KCl、维生素E和甲基-β-环糊精在内的许多药理学试剂能够在不同程度上防止25-OH-胆固醇诱导的细胞死亡。这些结果表明，胆固醇氧化物除了引起直接参与动脉粥样硬化的细胞的病理变化外，还可能诱导交感神经元的神经毒性。(C)1998年爱思唯尔科学公司
Cultured rat sympathetic neurons derived from postnatal rat superior cervical ganglia (SCG) were used to compare the neurotoxicity of several cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH-, and 25-OH-cholesterol. These agents caused an acute as well as a delayed toxicity-in sympathetic neurons with PB-OH-cholesterol appearing to be the most toxic. A time-dependent experiment indicated that PB-OH-cholesterol at 4 mu g/ml (10 mu M) was able to kill 50% of the cells in 36 h. Morphological studies indicate that most of the cells do not exhibit a structural change similar to that observed in neuronal programmed cell death, Whole-cell patch clamp recording of untreated controls and 2B-OH-cholesterol (2 mu g/ml)-treated cells indicated that this toxicity was not accompanied by significant changes in voltage-dependent calcium channel activity. A number of pharmacological agents including ethylene glycolbis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), cycloheximide, KCI, vitamin E, and methyl-beta-cyclodextrin were able to prevent the 25-OH-cholesterol-induced cell death to various degrees. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce neurotoxicity in sympathetic neurons. (C) 1998 Elsevier Science Inc.