過去的文獻指出很多種疾病與缺氧/缺血有關，如：癌症、中風等。最近的研究也證明了在缺血再灌流的情況下，會引發許多短暫性的基因調控，Sp1也在報導中指出可能參與在這樣的過程中。Sp1是重要的轉錄因子，它可以辨認GC-rich序列的啟動子，進而透過其轉錄活性調控下游基因的表現。在本篇研究中，我們發現在缺糖缺氧/中腦動脈阻塞之後，大腦皮質神經細胞的Sp1有堆積的情形，但是在神經膠質細胞則沒有堆積的現象。為了更進一步找出Sp1的堆積是透過哪些因素所導致，我們分別確認了Sp1 mRNA和蛋白質的穩定性，發現並沒有太大的變化，所以我們懷疑Sp1的堆積是透過轉譯效率提高所導致。在Polysome distribution assay的結果顯示，Sp1在缺糖缺氧之後轉譯效率有提高的情形，接著分析Sp1 5'-UTR，發現可能存在一個典型的IRES結構，利用bicistronic assay也證實了Sp1的堆積是透過IRES所導致。更進一步的，我們發現H2O2是引發Sp1堆積的重要因子。接著我們處理Sp1轉錄活性抑制劑mithramycin和Sp1 shRNA，在缺糖缺氧之後，神經細胞的存活率皆有顯著的下降，這也說明了，在缺血再灌流時Sp1的堆積對於神經細胞，扮演著保護性的角色。我們是第一個發現Sp1可以透過IRES-pathway造成Sp1的堆積，而對於中風之後的腦損傷，在治療上可能有所貢獻。

Hypoxia/ischemia is related to several diseases processing such as tumor and stroke. Recent studies demonstrate that ischemia-reperfusion induces a multitude of temporally regulated responses in gene expression, and some evidences suggested that Sp1 might be involved in these processes. Sp1 is one of the transcription factors which can specifically bind to GC-rich element in order to regulate the transcription activity of its target genes. In this study, we found that Sp1 was accumulated in cortical neurons of rats, but not in gilal cells under Oxygen Glucose Deprivation ( OGD ) condition and Middle Cerebral Artery Occlusion ( MCAO ) model. To more address this finding, the related experiments were carried out in vivo and in vitro. Data indicated that there is no significant difference in mRNA level of Sp1 and Sp1 stability under OGD condition. After analyzing the Sp1 DNA sequence within 5'-UTR and promoter region, we found one typical IRES-conserved sequence localizing within 5'-UTR of Sp1 genomic sequence. The reporter assay and polysome distribution assay revealed that Sp1 could be accumulated strongly and rapidly under hypoxia/ischemia neuron cells. Furthermore, H2O2 induced by OGD was the key factor to lead the Sp1 accumulation. Inhibition of Sp1 by mithramycin and knockdown of Sp1 by shRNA revealed that the Sp1 accumulation under ischemia-reperfusion leads to neuron cells survival. This is the first time to figure out that Sp1 could be induced through IRES-pathway, this finding might contribute the recovery of neurons after stroke.

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