Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion
Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion
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DOI：
10.1016/j.neuroscience.2006.12.011
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发表时间：
2007-03-16
期刊：
影响因子：
3.3
通讯作者：
Takamatsua, K.
中科院分区：
文献类型：
--
作者：
Masuo, Y.;Ogura, A.;Takamatsua, K.
海马钙蛋白是神经元钙敏感蛋白家族的一员，在海马锥体细胞中高度表达。最近，研究表明，海人酸全身注射后，海马阿蒙角（CA 3）区域CA 3区的神经元细胞死亡增加，而海马钙蛋白缺乏导致CA 3区神经元细胞死亡增加。用红藻氨酸处理导致CA 3中细胞死亡。在本研究中，我们注射喹啉酸，这是一种N-甲基-D-天冬氨酸受体激动剂，到海马区CA 1的阿蒙的角（CA 1）区在海马钙蛋白基因敲除（-/-）小鼠，一个程序，模拟短暂缺血。尽管注射后24 h在野生型（+/+）小鼠的注射部位观察到显著的固缩变化，但固缩细胞的区域在-/-小鼠的整个海马中延伸。Nissl染色切片中细胞数量的定量表明-/-小鼠中的细胞损伤比+/+小鼠中的细胞损伤更严重。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-生物素缺口末端标记阳性细胞的密度大致与Nissl染色的固缩细胞的密度相同。海马神经元的原代培养显示，在培养7天后，来自-/-小鼠的存活神经元的数量小于来自+/+小鼠的数量。单细胞内钙离子浓度的测定表明，-/-神经元的钙离子排出速度比+/+神经元慢。使用表达钙调素的COS 7细胞证实了钙调素参与钙分泌的维持。这些结果表明，海马钙蛋白在钙从神经元中挤出中起着重要作用，反过来，有助于保护它们免受海马中钙依赖性兴奋性毒素损伤。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Hippocalcin, which is a member of the neuronal calcium-sensor protein family, is highly expressed in hippocampal pyramidal cells. Recently, it was demonstrated that hippocalcin deficit caused an increase in neuronal cell death in the field CA3 of Ammon's horn (CA3) region of the hippocampus following the systemic injection of kainic acid. Treatment with kainic acid results in seizure-induced cell death in CA3. In the present study, we injected quinolinic acid, which is an N-methyl-D-aspartate receptor agonist, into the hippocampal field CA1 of Ammon's horn (CA1) region in hippocalcin-knockout (-/-) mice, a procedure which mimics transient ischemia. Although significant pyknotic changes were observed at the injected site in wild-type (+/+) mice 24 h after injection, the area of pyknotic cells extended throughout the hippocampus in -/- mice. The quantification of cell numbers in Nissl-stained sections indicated that the cell damage in -/- mice was more severe than that in +/+ mice. The density of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling-positive cells roughly paralleled that of Nissl-stained pyknotic cells. Primary cultures of hippocampal neurons showed that the number of surviving neurons from -/- mice after 7 days in culture was smaller than the number from +/+ mice. The measurement of intracellular calcium concentrations in single cells revealed that the calcium extrusion from -/- neurons was slower than that from +/+ neurons. The involvement of hippocalcin in the upkeep of calcium extrusion was confirmed using hippocalcin-expressing COS7 cells. These results suggest that hippocalcin plays an important role in calcium extrusion from neurons and, in turn, helps to protect them against calcium-dependent excitotoxin damage in the hippocampus. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.