Intrastriatal injection of dopamine results in DNA damage and apoptosis in rats
Intrastriatal injection of dopamine results in DNA damage and apoptosis in rats
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DOI：
10.1097/00001756-199808030-00026
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发表时间：
1998-08-03
期刊：
影响因子：
1.7
通讯作者：
Roth, GS
中科院分区：
文献类型：
--
作者：
Hattori, A;Luo, YQ;Roth, GS
纹状体中神经递质多巴胺(DA)的溢出参与了缺血、缺氧和局部暴露于高浓度兴奋性氨基酸的神经退行性变过程。然而，DA是如何引起神经毒性的还不清楚。用末端脱氧核苷酸转移酶催化的dUTP-生物素缺口标记(TUNEL)和Klenow聚合酶催化的[P-32]dCTP标记的DNA梯形图显示，纹状体内注射DA(0.5mU/mU/mW·L)可显著增加细胞的凋亡率。DA诱导细胞凋亡的特征是染色质浓缩、DNA片段化、皱缩和形状不规则。DA诱导的细胞死亡不是由于高渗液的作用，因为纹状体内注射相同浓度的氯化钠在同一大鼠的大脑两侧显示很少的TUNEL阳性标记。凋亡细胞的数量与DA的含量和暴露时间的长短成正比。DA浓度在0~1 mU/亩L时，染毒24 h后，浓度为1 mU/亩L的毒性效应最大。在体内证实DA诱导的细胞凋亡可能为DA神经毒性提供了潜在的分子机制。(C)1998年Rapid Science Ltd.
OVERFLOW Of the neurotransmitter dopamine (DA) in striatum is implicated in the neurodegenerative processes in ischemia, hypoxia and local exposure to high concentrations of excitatory amino acids. However, how DA causes neurotoxicity is not understood. We report that intrastriatal injection of DA (0.5-1 mu mol/mu l) in Wistar rats produces a robust increase in apoptotic cell death as determined by both a terminal deoxynucleotidyl transferase catalyzed dUTP-biotin nick labeling (TUNEL) and Klenow polymerase catalyzed [P-32]dCTP labeled DNA ladder. Cells in which apoptosis was induced by DA are characterized by condensed chromatin, DNA fragmentation, shrinkage and irregular shapes. The apoptotic cell death induced by DA is not due to the effect of hyperosmolar solution since intrastriatal injection of identical concentrations of NaCl on opposite sides of the same rat brains shows little TUNEL-positive labeling. The number of apoptotic cells is proportional to the amount of DA and length of exposure period. With DA concentrations from 0 to 1 mu mol/mu l, the maximal toxic effect appears at a concentration of 1 mu mol/mu l after 24 h exposure. Demonstration of DA-induced apoptosis in vivo may provide a potential molecular mechanism for DA neurotoxicity. (C) 1998 Rapid Science Ltd.