The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma cells
The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma cells
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DOI：
10.1016/s0006-8993(98)01274-8
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发表时间：
1999-02-06
期刊：
影响因子：
2.9
通讯作者：
Rao, ML
中科院分区：
文献类型：
--
作者：
Kölsch, H;Lütjohann, D;Rao, ML
神经退行性疾病的特征是神经细胞大量损失。神经元细胞死亡伴随着胆固醇释放增加以及胆固醇转化为极性代谢物24-羟基胆固醇(24-OH-Chol)，这似乎是中枢神经系统中消除大脑中胆固醇的重要机制。我们通过记录细胞形态、台盼蓝排除、LDH 释放到培养基中、细胞内钙和活性氧 (ROS) 来测试 24-OH-Chol 对 SH-SY5Y 人神经母细胞瘤细胞的影响。将 SH-SY5Y 人神经母细胞瘤细胞暴露于 50 μM 24-OH-Chol 中，导致细胞活力在 30 小时内损失 90%，24 小时后释放到培养基中的 LDH 迅速增加，24 至 30 小时后，我们发现细胞内钙含量升高。这些结果表明，在生理浓度范围内，24-OH-Chol会损害神经元细胞，因此我们推测这种氧甾醇可能参与神经退行性疾病的病因学。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Neurodegenerative disorders are characterized by a massive loss of nerve cells. The neuronal cell death is accompanied by an increased cholesterol release and conversion of cholesterol into the polar metabolite, 24-hydroxycholesterol (24-OH-Chol), appears to be an important mechanism in the central nervous system for eliminating cholesterol from the brain. We tested the influence of 24-OH-Chol on SH-SY5Y human neuroblastoma cells by recording cell morphology, Trypan blue exclusion, LDH-release into the culture medium, intracellular calcium and reactive oxygen species (ROS). The exposure of SH-SY5Y human neuroblastoma cells to 50 mu M 24-OH-Chol led to a 90% loss in cell viability within 30 h, the LDH-release into the medium increased rapidly after 24 h, and after 24 to 30 h we found an elevation in intracellular calcium. These results show that, in a physiological concentration range, 24-OH-Chol damages neuronal cells, thus we speculate that this oxysterol may be involved in the etiology of neurodegenerative disease. (C) 1999 Elsevier Science B.V. All rights reserved.