Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex.
Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex.
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DOI：
10.1186/1742-2094-2-16
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发表时间：
2005-07-26
影响因子：
9.3
通讯作者：
Brew BJ
中科院分区：
文献类型：
--
作者：
Guillemin GJ;Wang L;Brew BJ
有证据表明，犬尿氨酸途径 (KP)，特别是其最终产物之一喹啉酸 (QUIN) 在几种主要神经炎症性疾病，尤其是艾滋病痴呆症 (ADC) 的发病机制中发挥作用。我们推测QUIN可能参与星形胶质细胞凋亡，因为：1）在ADC患者的大脑中观察到凋亡的星形胶质细胞，2）ADC患者脑脊液QUIN浓度升高，3）QUIN可以诱导星形胶质细胞死亡。用三种病理生理浓度的 QUIN 处理人胎儿星形胶质细胞的原代培养物。使用双重免疫细胞化学评估活性 caspase 3 表达和细胞核浓缩的凋亡细胞计数。我们发现用 QUIN 处理人星形胶质细胞会诱导细胞凋亡的形态学（细胞体缩小）和生化变化（细胞核浓缩和活性 caspase 3 的过度表达）。分别用 500 nM 和 1200 nM QUIN 处理 24 小时后，10% 和 14% 的星形胶质细胞发生凋亡。预计这将导致营养支持因子相对缺乏，从而导致神经元功能障碍并可能导致死亡。 QUIN 诱导的星形胶质细胞凋亡为 ADC 期间 QUIN 的神经毒性提供了另一种潜在机制。
There is evidence that the kynurenine pathway (KP) and particularly one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC). We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1) apoptotic astrocytes have been observed in the brains of ADC patients, 2) ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3) QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking) and biochemical changes (nucleus condensation and over-expression of active caspase 3) of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.
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影响因子：
2.9
作者：
Dihné, M;Block, F;Töpper, R
通讯作者：
Töpper, R
影响因子：
5.1
作者：
Conti, F;Minelli, A;Melone, M
通讯作者：
Melone, M
影响因子：
11.2
作者：
BREW, BJ;ROSENBLUM, M;PRICE, RW
通讯作者：
PRICE, RW
影响因子：
3.7
作者：
Guillemin, GJ;Kerr, SJ;Brew, BJ
通讯作者：
Brew, BJ
影响因子：
14.5
作者：
HEYES, MP;SAITO, K;TOURTELLOTTE, WW
通讯作者：
TOURTELLOTTE, WW