Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Pharmacol Ther. 2010 Feb;125(2):260-85. doi: 10.1016/j.pharmthera.2009.10.009. Epub 2009 Nov 25.
Chronic low-level polychlorinated biphenyl (PCB) exposures remain a significant public health concern since results from epidemiological studies indicate that PCB burden is associated with immune system dysfunction, cardiovascular disease, and impairment of the developing nervous system. Of these various adverse health effects, developmental neurotoxicity has emerged as a particularly vulnerable endpoint in PCB toxicity. Arguably the most pervasive biological effects of PCBs could be mediated by their ability to alter the spatial and temporal fidelity of Ca2+ signals through one or more receptor-mediated processes. This review will focus on our current knowledge of the structure and function of ryanodine receptors (RyRs) in muscle and nerve cells and how PCBs and related non-coplanar structures alter these functions. The molecular and cellular mechanisms by which non-coplanar PCBs and related structures alter local and global Ca2+ signaling properties and the possible short and long-term consequences of these perturbations on neurodevelopment and neurodegeneration are reviewed.
慢性低水平多氯联苯 (PCB) 暴露仍然是一个重大的公共卫生问题，因为流行病学研究的结果表明 PCB 负荷与免疫系统功能障碍、心血管疾病和发育中神经系统受损有关。在这些各种不良健康影响中，发育神经毒性已成为 PCB 毒性的一个特别脆弱的终点。可以说，PCBs 最普遍的生物学效应可能是通过一种或多种受体介导的过程来改变 Ca2+信号的时空保真度来介导的。这篇综述将重点介绍我们目前对肌肉和神经细胞中肌浆网钙释放通道 (RyR) 的结构和功能的了解，以及 PCBs 和相关非平面结构如何改变这些功能。非平面 PCB 和相关结构改变局部和全局 Ca2+信号特性的分子和细胞机制，以及这些干扰对神经发育和神经退行性变的短期和长期后果，都进行了综述。
