Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat.
Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat.
复制标题
大鼠局灶性脑缺血后核孔复合蛋白的动态错误定位。
DOI：
10.1002/jnr.24005
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Abe K.
中科院分区：
文献类型：
--
作者：
Li Q;Ohta Y;Yamashita T;Shang J;Deguchi K;Feng T;Sato K;Hishikawa N;Nakano Y;Abe K.
核孔复合物（Nuclear pore complex，NPC）在协调蛋白质和核酸在细胞核和细胞质之间的转运中起重要作用，因此对于维持正常的细胞功能和可靠性至关重要。在本研究中，我们研究了NPC的五种代表性组分的时间免疫组织化学分布-RanGap 1（RanGap 1），糖蛋白-210（Gp 210），核孔蛋白205（Nup 205），核孔蛋白107（Nup 107），和核孔蛋白50（Nup 50）-在大鼠脑中短暂大脑中动脉闭塞（tMCAO）后90分钟至再灌注后28天。单次免疫组织化学分析显示，在假手术对照组大脑中，沿着核的外周沿着出现环状染色。tMCAO后，Gp 210和Nup 107免疫反应性从第1天开始持续增加，RanGap 1、Nup 205和Nup 50从第2天开始增加，直到第28天，这也显示出在缺血区域的细胞核内进行性沉淀，而缺血核心显示出缺乏表达，结构塌陷。双重免疫荧光分析显示核保留和RanGap 1与Nup 205、Gp 210与Nup 205以及Nup 205与Nup 107的部分共定位;上述大部分缺血性变化与C9 orf 72遗传性肌萎缩侧索硬化患者中观察到的相似。总之，这些观察结果表明，这些核孔蛋白的错误定位可能是缺血性和神经退行性疾病的共同发病机制。© 2016 Wiley Periodicals，Inc.
Nuclear pore complexes (NPCs) play an important role in coordinating the transport of proteins and nucleic acids between the nucleus and cytoplasm, and are therefore essential for maintaining normal cellular function and liability. In the present study, we investigated the temporal immunohistochemical distribution of five representative components of NPCs—Ran GTPase‐activating protein 1 (RanGap1), glycoprotein‐210 (Gp210), nucleoporin 205 (Nup205), nucleoporin 107 (Nup107), and nucleoporin 50 (Nup50)—after 90 min of transient middle cerebral artery occlusion (tMCAO) up to 28 days after the reperfusion in rat brains. Single immunohistochemical analyses showed ring‐like stainings along the periphery of the nucleus in sham control brains. After tMCAO, Gp210 and Nup107 immunoreactivity continuously increased from 1 day, and RanGap1, Nup205, and Nup50 increased from 2 days until 28 days, which also displayed progressive precipitations within the nucleus in the peri‐ischemic area, while the ischemic core showed scarce expression with collapsed structure. Double immunofluorescent analyses revealed nuclear retention and apparent colocalization of RanGap1 with Nup205, Gp210 with Nup205, and partial colocalization of Nup205 with Nup107; most of the ischemic changes above were similar to those observed in patients with C9orf72‐genetic amyotrophic lateral sclerosis. Taken together, these observations suggest that the mislocalization of these nucleoporins may be a common pathogenesis of both ischemic and neurodegenerative disease. © 2016 Wiley Periodicals, Inc.