Ho B K, Alexianu M E, Colom L V, Mohamed A H, Serrano F, Appel S H
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6796-801. doi: 10.1073/pnas.93.13.6796.
Calbindin-D28K and/or parvalbumin appear to influence the selective vulnerability of motoneurons in amyotrophic lateral sclerosis (ALS). Their immunoreactivity is undetectable in motoneurons readily damaged in human ALS, and in differentiated motoneuron hybrid cells [ventral spinal cord (VSC 4.1 cells)] that undergo calcium-dependent apoptotic cell death in the presence of ALS immunoglobulins. To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were infected with a retrovirus carrying calbindin-D28K cDNA under the control of the promoter of the phosphoglycerate kinase gene. Differentiated calbindin-D28K cDNA-infected cells expressed high calbindin-D28K and demonstrated increased resistance to ALS IgG-mediated toxicity. Treatment with calbindin-D28K antisense oligodeoxynucleotides, which significantly decreased calbindin-D28K expression, rendered these cells vulnerable again to ALS IgG toxicity.
钙结合蛋白-D28K和/或小白蛋白似乎影响肌萎缩侧索硬化症（ALS）中运动神经元的选择性易损性。在人类ALS中容易受损的运动神经元以及在存在ALS免疫球蛋白的情况下经历钙依赖性凋亡细胞死亡的分化运动神经元杂交细胞[腹侧脊髓（VSC 4.1细胞）]中，无法检测到它们的免疫反应性。为了提供钙结合蛋白在运动神经元易损性中作用的额外证据，用携带在磷酸甘油酸激酶基因启动子控制下的钙结合蛋白-D28K cDNA的逆转录病毒感染VSC 4.1细胞。分化的钙结合蛋白-D28K cDNA感染细胞表达高水平的钙结合蛋白-D28K，并表现出对ALS IgG介导的毒性的抗性增加。用钙结合蛋白-D28K反义寡脱氧核苷酸处理，显著降低了钙结合蛋白-D28K的表达，使这些细胞再次易受ALS IgG毒性的影响。
