SPECIFIC REDUCTION OF CALCIUM-BINDING PROTEIN (28-KILODALTON CALBINDIN-D) GENE-EXPRESSION IN AGING AND NEURODEGENERATIVE DISEASES
SPECIFIC REDUCTION OF CALCIUM-BINDING PROTEIN (28-KILODALTON CALBINDIN-D) GENE-EXPRESSION IN AGING AND NEURODEGENERATIVE DISEASES
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DOI：
10.1073/pnas.87.11.4078
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
CHRISTAKOS, S
中科院分区：
文献类型：
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作者：
IACOPINO, AM;CHRISTAKOS, S
目前的研究证实，在衰老和神经退行性疾病中，神经元钙结合蛋白（28-kDa 钙结合蛋白-D）基因表达存在特定的显着降低。通过用钙调蛋白、亲环蛋白和 B-肌动蛋白 cDNA 重新检测印迹来测试钙结合蛋白 mRNA 水平中观察到的变化的特异性。衰老大鼠的大体大脑区域显示出小脑、纹状体和脑干区域钙结合蛋白 mRNA 和蛋白质水平的特异性显着降低 (60-80%)，但大脑皮层或海马体中却没有。衰老人脑的离散区域中，小脑、纹状体和基底核中的钙结合蛋白和 mRNA 显着减少 (50-88%)，但新皮质、海马、杏仁核、蓝斑或中缝背核中则没有。将患病的人脑组织与年龄和性别匹配的对照进行比较，发现黑质（帕金森病）、纹状体（亨廷顿病）、基底核（阿尔茨海默病）以及海马和中缝背核（帕金森病、亨廷顿病和阿尔茨海默病）的钙结合蛋白和 mRNA 显着下降（60-88%），但在小脑、新皮质、杏仁核或蓝斑。由于钙结合蛋白基因表达在已知特别受衰老和每种神经退行性疾病影响的大脑区域中特异性降低，因此这些发现表明钙结合蛋白基因表达降低可能导致钙缓冲或神经元内钙稳态失败，从而导致衰老过程中和神经退行性疾病发病机制中钙介导的细胞毒性事件。
The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodengenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbinin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50-88%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60-88%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Hungtington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.