Phosphorylation of retinoblastoma protein in rat brain after transient middle cerebral artery occlusion
Phosphorylation of retinoblastoma protein in rat brain after transient middle cerebral artery occlusion
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DOI：
10.1046/j.1365-2990.2000.00264.x
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发表时间：
2000-08-01
影响因子：
5
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Hayashi, T;Sakai, K;Abe, K
虽然成熟的神经元不复制基因组DNA，但缺血后神经元中的一些细胞周期相关激酶被异常激活。视网膜母细胞瘤（retinoblastoma，Rb）蛋白的过度磷酸化是有丝分裂信号级联反应的共同途径，本研究观察了大脑中动脉（middle cerebral artery，MCA）阻断后大鼠脑内Rb蛋白的磷酸化状态及其mRNA水平。免疫组织化学分析显示，神经元在假手术的大脑表达Rb蛋白没有过度磷酸化的形式。缺血后1小时至3天，大脑中动脉区域的神经元中Rb蛋白的过度磷酸化形式的免疫反应性逐渐增加。Western blot分析显示了类似的变化。逆转录-聚合酶链反应（RT-PCR）结果显示Rb在mRNA水平上无明显变化。这些结果表明，Rb蛋白进行性过度磷酸化脑缺血后，这可能会激活脑缺血后神经元细胞的凋亡机制。
Although mature neurones do not replicate genomic DNA, some cell cycle-related kinases are aberrantly activated in neurones after ischaemia. As hyperphosphorylation of retinoblastoma (Rb) protein is the common pathway in mitotic signal cascade, this study investigated the phosphorylation state of the Rb protein as well as its mRNA level in rat brain after transient middle cerebral artery (MCA) occlusion. Immunohistochemical analysis revealed that neurones in the sham-operated brain expressed Rb protein without the hyperphosphorylated form. Immunoreactivity for the hyperphosphorylated form of Rb protein progressively increased from 1 h to 3 days after ischaemia in neurones in the MCA territory. Western blot analysis demonstrated similar change. However, reverse transcription-polymerase chain reaction study revealed that Rb showed no definite change at the mRNA level. These results suggest that Rb protein is progressively hyperphosphorylated in the brain after ischaemia, which may activate apoptotic mechanisms in neuronal cells of the brain after ischaemia.