Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum
Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum
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DOI：
10.1016/j.toxlet.2004.12.011
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发表时间：
2005-04-28
影响因子：
3.5
通讯作者：
Kodavanti, PRS
中科院分区：
文献类型：
--
作者：
Lehmler, HJ;Robertson, LW;Kodavanti, PRS
有证据表明，具有邻位氯取代基的多氯联苯同系物有可能导致神经毒性。许多涉及这些神经毒性效应的多氯联苯同系物是手性的。目前尚不清楚手性多氯联苯同系物的对映异构体是否具有不同的神经毒性作用。本文报道了外消旋2，2 '，3，3'，6-五氯联苯（PCB 84）及其对映体对两种神经化学指标的影响，即小脑颗粒细胞[H-3]佛波醇酯结合测定的蛋白激酶C（PKC）易位和成年大鼠小脑微粒体Ca-45（2+）摄取测定的Ca ~（2+）螯合。（+）-和（-）-PCB 84均以浓度依赖性方式增加[H-3]-佛波酯结合，（-）-PCB 84的作用略强。外消旋PCB 84比单独的纯对映体显著更有效。(-)-和（+）-PCB 84均能抑制细胞内Ca-45（2+）-的摄取，但外消旋PCB 84的作用更强。这些结果表明，PCB 84对映体单独可以有不同的效力，这些可能不同于外消旋混合物，观察可能有重要的意义，了解手性PCB同系物的神经毒性机制。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
There is evidence that polychlorinated biphenyl (PCB) congeners with ortho chlorine substituents have potential to cause neurotoxicity. Many PCB congeners implicated in these neurotoxic effects are chiral. It is currently unknown if the enantiomers of chiral PCB congeners have different neurotoxic effects. We herein report the effect of racemic 2,2',3,3',6-pentachlorobiphenyl (PCB 84) and its enantiorners on two neurochernical measures, protein kinase C (PKC) translocation as determined by [H-3]phorobol ester binding in cerebellar granule cells and Ca2+-sequestration as determined by Ca-45(2+)-uptake by microsomes isolated from adult rat cerebellum. Both (+)- and (-)-PCB 84 increased [H-3]-phorobol ester binding in a concentration-dependent manner with (-)-PCB 84 being slightly more potent. Racemic PCB 84 was significantly more potent and efficacious than the pure enantiomers alone. (-)- and (+)-PCB 84 each inhibited microsornal Ca-45(2+)-uptake to a similar extent, whereas racemic, PCB 84 was more potent and efficacious. These results indicate that PCB 84 enantionlers alone can have different potencies, and these may differ from that of the racemic mixture, observations that may have important implications for understanding the mechanisms of neurotoxicity of chiral PCB congeners. (c) 2005 Elsevier Ireland Ltd. All rights reserved.