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Histochemical Mapping of hnRNP A2/B1 in Rat Brain After Ischemia–Reperfusion Insults

机译:大鼠脑缺血再灌注后hnRNP A2 / B1的组织化学定位

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摘要

Cerebral ischemia–reperfusion (I/R) insults result in neuronal cell death, brain tissue loss, and severe neurological deficits. However, the underlying mechanism is still not fully understood. Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 belongs to a family of RNA-binding proteins that plays a central role in pre-mRNA processing. Recent studies have revealed that hnRNP A2/B1 may be involved in the progress of I/R; therefore, the present study aimed to examine expression patterns of hnRNP A2/B1 to better understand posttranscriptional regulations in cerebral I/R insults. Focal cerebral I/R models were induced by right middle cerebral artery occlusion (MCAO) for 120 min followed by 3, 6, 12, 24, 48, and 72 hr of reperfusion in male Sprague-Dawley rats. We employed immunohistochemistry to examine expression of hnRNP A2/B1 in rat cerebral cortex (including cingulate cortex, striate cortex, temporal cortex, and piriform cortex) and hippocampus after I/R insults. Results showed that expression of hnRNP A2/B1 was significantly downregulated in cerebral cortex and hippocampus from 3 to 24 hr of reperfusion after MCAO for 120 min, but significantly upregulated at 48 hr of reperfusion. Unexpectedly, translocation of hnRNP A2/B1 from nucleus to cytoplasm and even to neurites was observed in cerebral cortex at 3 hr of reperfusion, reaching a peak at 24 hr of reperfusion, but not in hippocampus, indicating different posttranscriptional regulation patterns in different brain regions. Interestingly, translocation of hnRNP A2/B1 was only observed in cerebral cortex with MCAO but not in the opposite side, suggesting an I/R–specific expression pattern in the brain. Our data suggest that hnRNP A2/B1 participates in posttranscriptional regulation of neurons in cerebral cortex and hippocampus that suffered I/R insults, although posttranscriptional regulation is more extensive in neuronal cells of cerebral cortex than in hippocampus. >(J Histochem Cytochem 58:695–705, 2010)
机译:脑缺血再灌注(I / R)损伤会导致神经元细胞死亡,脑组织损失和严重的神经功能缺损。但是,底层机制仍未完全理解。异质核核糖核蛋白(hnRNP)A2 / B1属于RNA结合蛋白家族,在前mRNA加工中起着核心作用。最近的研究表明,hnRNP A2 / B1可能与I / R的进展有关。因此,本研究旨在检查hnRNP A2 / B1的表达模式,以更好地了解脑I / R损伤的转录后调控。在雄性Sprague-Dawley大鼠中,通过右脑中动脉闭塞(MCAO)诱导120分钟,然后进行3、6、12、24、48和72小时的再灌注来诱导局灶性I / R模型。我们采用免疫组化技术检测了I / R损伤后hnRNP A2 / B1在大鼠大脑皮层(包括扣带状皮层,条纹状皮层,颞叶皮层和梨状皮层)和海马中的表达。结果表明,MCAO后120分钟,再灌注3至24小时,hnRNP A2 / B1在大脑皮层和海马中的表达显着下调,而在再灌注48小时时,其表达显着上调。出乎意料的是,在再灌注3小时时,大脑皮层中发现hnRNP A2 / B1从核向胞质移位,甚至到神经突,在再灌注24小时时达到峰值,但在海马中却没有,这表明不同脑区的转录后调控方式不同。有趣的是,hnRNP A2 / B1仅在带有MCAO的大脑皮层中观察到移位,而在相反侧则未观察到,这表明脑中I / R特异性表达模式。我们的数据表明,hnRNP A2 / B1参与遭受I / R损伤的大脑皮层和海马中神经元的转录后调控,尽管转录后的调控在大脑皮层神经元细胞中比在海马中更为广泛。 >(J Histochem Cytochem 58:695-705,2010)

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