Bano D, Munarriz E, Chen H L, Ziviani E, Lippi G, Young K W, Nicotera P
MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road LE1 9HN, Leicester, UK.
Ann N Y Acad Sci. 2007 Mar;1099:451-5. doi: 10.1196/annals.1387.006.
Neurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca2+ deregulation leading to necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+ extrusion pathway is a lethal event in multiple forms of cell death.
神经退行性疾病通常涉及神经元连接丧失、突触功能障碍伴过度修剪以及离子失衡。这些情况往往是细胞死亡的前奏，其途径要么是通过激活凋亡或坏死死亡程序，要么是过度自噬。在许多情况下，局部或全身性的Ca2+失调参与信号传导或执行细胞死亡。我们最近发现，在脑缺血以及由过量谷氨酸引发的兴奋性毒性过程中，导致坏死的不可逆Ca2+失调是由于钙蛋白酶介导的质膜Na+/Ca2+交换体（NCX）调节所致。在此我们表明，在经历凋亡的神经元中，半胱天冬酶也可切割NCX，这表明主要Ca2+外排途径的切割是多种形式细胞死亡中的致死事件。
