p53 mediated transcription of Omi/HtrA2 in aging myocardium
p53 mediated transcription of Omi/HtrA2 in aging myocardium
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p53 介导的 Omi/HtrA2 在衰老心肌中的转录
DOI：
10.1016/j.bbrc.2019.09.062
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Liu Huirong
中科院分区：
文献类型：
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作者：
Wu Linguo;Liu Dan;Wu Ye;Wei Xin;Wang Zhaojia;Wang Wen;Zhang Suli;Yang Hong;Yi Ming;Liu Huirong
目的Omi/HtrA 2是一种促凋亡蛋白，衰老心肌中Omi/HtrA 2的mRNA和蛋白水平增加促进细胞凋亡并影响线粒体稳态。我们前期的研究发现p53可以与Omi/HtrA 2启动子结合。本研究旨在探讨p53是否参与了衰老心肌Omi/HtrA 2蛋白表达的调节。方法和结果采用Western blot方法检测衰老心肌Omi/HtrA 2和p53核蛋白的表达，发现二者在衰老心肌中均升高。此外，我们还观察到p53与Omi/HtrA 2启动子的结合增加，通过染色质免疫沉淀。为初步探讨Omi/HtrA 2的调控机制，分别采用质粒转染和RNA干扰的方法上调或敲低p53基因。Real-time PCR和Western blot结果显示，Omi/HtrA 2的mRNA和蛋白水平随着p53的过表达而升高，转染pcDNA3.1-p53后Omi/HtrA 2启动子活性增强。RNA干扰的结果与此相反，我们的研究表明，衰老心肌p53与Omi/HtrA 2启动子的结合能力增强，p53通过增强Omi/HtrA 2的启动子活性而促进Omi/HtrA 2的mRNA和蛋白表达。这些结果为探讨Omi/HtrA 2在心脏衰老过程中的作用机制提供了新的思路。
AimsOmi/HtrA2 is a pro-apoptotic protein, increased mRNA and protein levels of Omi/HtrA2 in aging myocardium facilitates apoptosis and affects mitochondrial homeostasis. Our previous study found that p53 can bind to the Omi/HtrA2 promoter. The purpose of this study was to determine whether p53 participates in regulating the expression of Omi/HtrA2 in aging myocardium.Methods and resultswe used Western blot to detect the expression of Omi/HtrA2 and p53 nucleoprotein, and then found that both of them were elevated in aging heart. Furthermore, we also observed the increased binding of p53 to Omi/HtrA2 promoter by chromatin immunoprecipitation. To initially explore the regulation mechanism of Omi/HtrA2, plasmid transfection and RNA interference in NIH3T3 cells were used to upregulate or knock down p53, respectively. The mRNA and protein levels of Omi/HtrA2 were increased with the overexpression of p53 by real-time PCR and Western blot, and Omi/HtrA2 promoter activity enhanced after transfected with pcDNA3.1-p53. The result from RNA interference was quite the contrary.Our study demonstrated that the binding ability of p53 to Omi/HtrA2 promoter was increased in aging myocardium, and increased p53 promoted the mRNA and protein levels of Omi/HtrA2 by enhancing the promoter activity of Omi/HtrA2.Conclusionsp53 acts as a transcriptional factor that induces Omi/HtrA2 expression in aged cardiomyocytes.These results provide a new way to explore the mechanism of increased Omi/HtrA2 in the aging process of heart.