Guo Hongfeng, Tian Yi, Lu Hai, Wei Yong, Ying Dajun
Department of Anatomy, Third Military Medical University, Sha-Ping-Ba District, Chongqing, China.
J Biomed Biotechnol. 2010;2010. doi: 10.1155/2010/168689. Epub 2010 Jul 14.
Heme oxygenase-1 (HO-1) is well known as a cytoprotective factor. Research has revealed that it is a promising therapeutic target for cardiovascular diseases. In the current study, an HMOX1 (HO-1 gene) enhancer-specific artificial zinc-finger protein (AZP) was designed using bioinformatical methods. Then, an artificial transcription factor (ATF) was constructed based on the AZP. In the ATF, the p65 functional domain was used as the effector domain (ED), and a nuclear localization sequence (NLS) was also included. We next analyzed the affinity of the ATF to the HMOX1 enhancer and the effect of the ATF on endogenous HMOX1 expression. The results suggest that the ATF could effectively upregulate endogenous HMOX1 expression in ECV304 cells. With further research, the ATF could be developed as a potential drug for cardiovascular diseases.
血红素加氧酶-1(HO-1)作为一种细胞保护因子广为人知。研究表明,它是心血管疾病一个很有前景的治疗靶点。在本研究中,利用生物信息学方法设计了一种HMOX1(HO-1基因)增强子特异性人工锌指蛋白(AZP)。然后,基于该AZP构建了一种人工转录因子(ATF)。在该ATF中,p65功能域用作效应域(ED),并且还包含一个核定位序列(NLS)。接下来,我们分析了该ATF对HMOX1增强子的亲和力以及该ATF对内源性HMOX1表达的影响。结果表明,该ATF能够有效上调ECV304细胞中的内源性HMOX1表达。随着进一步研究,该ATF有望开发成为心血管疾病的潜在药物。