Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.
Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1-mediated cytoprotection.
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Mipu1 是一种新型直接靶基因，参与缺氧诱导因子 1 介导的细胞保护。
DOI：
10.1371/journal.pone.0082827
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Wang K;Lei J;Zou J;Xiao H;Chen A;Liu X;Liu Y;Jiang L;Xiao Z;Xiao X
心肌缺血预适应上调蛋白1（myocardial ischemic preconditioning up-regulated protein 1，Mipu 1）是本实验室新近发现的一种新的锌指转录因子，在心肌缺血预适应过程中表达上调。然而，目前尚不清楚是什么转录因子促成其诱导表达。在本研究中，我们报道了HIF-1调节Mipu 1的诱导表达，Mipu 1通过抑制Bax表达参与HIF-1α抗氧化应激的细胞保护作用。我们的研究结果表明，Mipu 1的诱导表达与转录因子HIF-1的表达和激活有关，如氯化钴（CoCl 2）处理，HIF-1α过表达和敲低实验所示。EMSA和荧光素酶报告基因分析表明，HIF-1α与Mipu 1启动子区的缺氧反应元件（HRE）结合，促进Mipu 1的转录。此外，我们的研究结果表明，Mipu 1抑制Bax的表达，一个重要的促凋亡蛋白与细胞凋亡的内在途径，提高细胞保护HIF-1对过氧化氢（H2 O2）介导的损伤H9 C2细胞。Bax可能是转录因子Mipu 1的潜在靶基因，为理解HIF-1的细胞保护作用提供了新的思路，也为进一步阐明Mipu 1保护细胞免受病理应激的机制提供了新的线索。
Mipu1 (myocardial ischemic preconditioning up-regulated protein 1), recently identified in our lab, is a novel zinc-finger transcription factor which is up-regulated during ischemic preconditioning. However, it is not clear what transcription factor contributes to its inducible expression. In the present study, we reported that HIF-1 regulates the inducible expression of Mipu1 which is involved in the cytoprotection of HIF-1α against oxidative stress by inhibiting Bax expression. Our results showed that the inducible expression of Mipu1 was associated with the expression and activation of transcription factor HIF-1 as indicated by cobalt chloride (CoCl2) treatment, HIF-1α overexpression and knockdown assays. EMSA and luciferase reporter gene assays showed that HIF-1α bound to the hypoxia response element (HRE) within Mipu1 promoter region and promoted its transcription. Moreover, our results revealed that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein associated with the intrinsic pathway of apoptosis, elevating the cytoprotection of HIF-1 against hydrogen peroxide (H2O2)-mediated injury in H9C2 cells. Our findings implied that Bax may be a potential target gene of transcription factor Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1 and new clues for further elucidating the mechanisms by which Mipu1 protects cell against pathological stress.
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DOI：
10.1126/science.1192811
发表时间：
2010-07-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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