Differential changes in phosphorylation of tau at PHF-1 and 12E8 epitopes during brain ischemia and reperfusion in gerbils
Differential changes in phosphorylation of tau at PHF-1 and 12E8 epitopes during brain ischemia and reperfusion in gerbils
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DOI：
10.1007/s11064-006-9199-3
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发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
Ksiezak-Reding, H.
中科院分区：
文献类型：
--
作者：
Gordon-Krajcer, W.;Kozniewska, E.;Ksiezak-Reding, H.
皮质神经元容易受到缺血性损伤，这可能导致细胞骨架变化和神经退行性变。 Tau 是一种在神经元和神经胶质细胞中表达的微管相关蛋白。我们检测了双侧颈总动脉闭塞引起的 5 分钟缺血，然后再灌注 20 分钟至 7 天期间沙鼠大脑皮质中 tau 蛋白的磷酸化状态。对照脑匀浆含有 63、65 和 68 kD tau 多肽，与针对非磷酸化 tau 表位产生的 Alz 50、Tau 14 和 Tau 46 抗体发生免疫反应。 Gerbil tau 还与一些（PHF-1 和 12E8）但不是所有（AT8、AT100、AT180 和 AT270）针对磷酸化 tau 表位的抗体发生免疫反应。 PHF-1 识别单个 68 kD 多肽，12E8 结合 63 kD 多肽。在 5 分钟缺血期间，PHF-1 免疫反应性下降至 6%，然后在血液再循环 20 分钟后恢复至对照水平，并随后在 3 天和 7 天后增加至高于对照值。相反，12E8 免疫反应性在缺血和再灌注期间保持稳定。我们的结果表明，tau 的两个磷酸化表位受到不同机制的调节，并且可能在微管动力学中发挥不同的作用。它们还可以定义易受缺血影响的各种神经元/神经胶质细胞池。
Cortical neurons are vulnerable to ischemic insult, which may cause cytoskeletal changes and neurodegeneration. Tau is a microtubule-associated protein expressed in neuronal and glial cells. We examined the phosphorylation status of tau protein in the gerbil brain cortex during 5 min ischemia induced by bilateral common carotid artery occlusion followed by reperfusion for 20 min to 7 days. Control brain homogenates contained 63, 65 and 68 kD polypeptides of tau immunoreactive with Alz 50, Tau 14 and Tau 46 antibodies raised against non-phosphorylated tau epitopes. Gerbil tau was also immunoreactive with some (PHF-1 and 12E8) but not all (AT8, AT100, AT180 and AT270) antibodies raised against phosphorylated tau epitopes. PHF-1 recognized a single 68 kD polypeptide and 12E8 bound the 63 kD polypeptide. During 5 min ischemia, PHF-1 immunoreactivity declined to 6%, then recovered to control levels after 20 min of blood recirculation and subsequently increased above control values 3 and 7 days later. In contrast, 12E8 immunoreactivity remained stable during ischemia and reperfusion. Our results suggest that the two phosphorylated epitopes of tau are regulated by different mechanisms and may play different roles in microtubule dynamics. They may also define various pools of neuronal/glial cells vulnerable to ischemia.