Ca(2+)-dependent processes as mediators of neurotoxicity.
Ca(2+)-dependent processes as mediators of neurotoxicity.
复制标题
Ca(2) 依赖性过程作为神经毒性的介质。
作者：
M. Verity
Ca 2+离子对细胞过程产生深远的影响，并了解细胞内Ca 2+稳态的控制机制，而复杂的是在此讨论的强制性。[Ca 2 +]i的长期持续增加作为神经毒素诱导的[Ca 2 +]i稳态不稳定的表现的鉴定和认识将与各种神经毒素诱导的细胞损伤相关。将确定毒物与位于神经元/神经胶质细胞膜和/或钙小体中的ATP调节的Ca 2+泵相互作用的位点; Ca 2+蛋白的可用性;线粒体Ca 2+储存机制的破坏;电压依赖性Ca 2+通道的触发和Na+/Ca 2+交换器的调节，并与推定的毒素作用相关。这些系统中的一个或多个的故障将导致离子化[Ca 2 +]i的持续升高--这是Ca 2+不稳定的反映。将鉴定由Ca 2+去稳定化产生的靶点，包括磷脂酶C活化、PLA 2活化、蛋白激酶C（PKC）易位和Ca（2+）依赖性钙蛋白酶1的活化。使用特定的神经毒性抑制剂，例如，天然鞘脂、鞘氨醇、PKC的下调、腺苷酸环化酶的抑制剂和激活剂以及抗蛋白酶剂将允许研究这些最终共同途径在神经毒性演变中的作用。
The Ca2+ ion exerts a profound influence on cellular processes and an understanding of control mechanisms of intracellular Ca2 homeostasis while complex is mandatory in this discussion. The identification and recognition of prolonged sustained increase in [Ca2+]i as a manifestation of neurotoxin-induced destabilization of [Ca2+]i homeostasis will be related to a variety of neurotoxicant-induced cell injuries. The sites of toxicant interaction with ATP-regulated Ca2+ pumps located in the neuronal/glial membrane and/or calciosomes; availability of Ca2+ proteins; disruption in mitochondrial mechanisms for Ca2+ storage; triggers of voltage-dependent Ca2+ channels and modulation of the Na+/Ca2+ exchanger will be identified and related to presumptive toxin action. Failure of one or more of these systems will result in continuous elevation of ionized [Ca2+]i--a reflection of Ca2+ destabilization. The targets resulting from Ca2+ destabilization will be identified, to include phospholipase C activation, PLA2 activation, protein kinase C (PKC) translocation, and activation of Ca(2+)-dependent calpain 1. The use of specific inhibitors of neurotoxicity, e.g., natural sphingolipids, sphingosine, down regulation of PKC, inhibitors and activators of adenylate cyclase, and antiprotease agents will allow for investigation of the role of these final common pathways in the evolution of neurotoxicity.