Solà C, Tusell J M, Serratosa J
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona, CSIC, Spain.
Neuroscience. 1997 May;78(1):155-64. doi: 10.1016/s0306-4522(96)00532-5.
In the central nervous system, many of the effects resulting from an increase in the intracellular levels of calcium are mediated by calmodulin, a major calcium-binding protein in the mammalian brain. Calmodulin is expressed by three different genes, namely CaM I, CaM II and CaM III, all of which encode an identical protein. We studied the expression of calmodulin in the mouse brain at different times after the administration of a convulsant dose of kainate, a potent neuroexcitotoxic agent. We detected the presence of the different calmodulin messenger RNAs and of the protein itself in brain sections by in situ hybridization histochemistry and immunocytochemistry respectively. In addition, we determined the calmodulin content in brain regions by radioimmunoassay. Kainate-treated animals did not show areas of neuronal death at the different times following administration considered. An increase in the hybridization signal for CaM I messenger RNAs was observed from 5 h after kainate administration in the different brain regions tested. In contrast, the CaM II messenger RNA signal decreased gradually to a minimum 24 h after treatment in the hippocampus, while the CaM III messenger RNA signal was mostly unaffected. Calmodulin immunoreactivity also increased in the hippocampus. Nevertheless, we did not detect any significant difference in calmodulin content between brain regions of control and treated animals by radioimmunoassay. Kainate treatment induced modifications in the expression of calmodulin at the level of both messenger RNAs and protein. The results suggest a differential regulation of the three calmodulin genes in the adult mouse brain and a post-transcriptional or a post-translational regulation of calmodulin expression.
在中枢神经系统中，细胞内钙水平升高所产生的许多效应是由钙调蛋白介导的，钙调蛋白是哺乳动物脑中一种主要的钙结合蛋白。钙调蛋白由三个不同的基因表达，即CaM I、CaM II和CaM III，所有这些基因都编码相同的蛋白质。我们研究了在给予惊厥剂量的红藻氨酸（一种强效神经兴奋毒性剂）后不同时间点小鼠脑中钙调蛋白的表达情况。我们分别通过原位杂交组织化学和免疫细胞化学检测了脑切片中不同钙调蛋白信使核糖核酸以及蛋白质本身的存在情况。此外，我们通过放射免疫测定法测定了脑区中的钙调蛋白含量。在考虑的给药后的不同时间点，经红藻氨酸处理的动物未显示出神经元死亡区域。在给药后5小时，在所测试的不同脑区中观察到CaM I信使核糖核酸的杂交信号增加。相反，在海马体中，CaM II信使核糖核酸信号在处理后24小时逐渐下降至最低水平，而CaM III信使核糖核酸信号大多未受影响。海马体中的钙调蛋白免疫反应性也增加了。然而，通过放射免疫测定法，我们未检测到对照动物和处理动物脑区之间钙调蛋白含量有任何显著差异。红藻氨酸处理诱导了钙调蛋白在信使核糖核酸和蛋白质水平上表达的改变。结果表明在成年小鼠脑中，三种钙调蛋白基因存在差异调节，并且钙调蛋白表达存在转录后或翻译后调节。
