过氧化物酶体增殖物激活受体γ（PPARγ）在原代神经元中通过转录调控胰岛素降解酶的表达。
PPARgamma transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons.
作者信息
Du Jing, Zhang Lang, Liu Shubo, Zhang Chi, Huang Xiuqing, Li Jian, Zhao Nanming, Wang Zhao
机构信息
Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, PR China.
出版信息
Biochem Biophys Res Commun. 2009 Jun 12;383(4):485-90. doi: 10.1016/j.bbrc.2009.04.047. Epub 2009 Apr 19.
Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a key role in degrading both Abeta and insulin and deficient in IDE function is associated with Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) pathology. However, little is known about the cellular and molecular regulation of IDE expression. Here we show IDE levels are markedly decreased in DM2 patients and positively correlated with the peroxisome proliferator-activated receptor gamma (PPARgamma) levels. Further studies show that PPARgamma plays an important role in regulating IDE expression in rat primary neurons through binding to a functional peroxisome proliferator-response element (PPRE) in IDE promoter and promoting IDE gene transcription. Finally, we demonstrate that PPARgamma participates in the insulin-induced IDE expression in neurons. These results suggest that PPARgamma transcriptionally induces IDE expression which provides a novel mechanism for the use of PPARgamma agonists in both DM2 and AD therapies.
胰岛素降解酶（IDE）是一种蛋白酶，已被证明在降解β淀粉样蛋白（Aβ）和胰岛素方面发挥关键作用，而IDE功能缺陷与阿尔茨海默病（AD）和2型糖尿病（DM2）的病理过程相关。然而，关于IDE表达的细胞和分子调控知之甚少。在此我们发现，DM2患者体内IDE水平显著降低，且与过氧化物酶体增殖物激活受体γ（PPARγ）水平呈正相关。进一步研究表明，PPARγ通过与IDE启动子中的功能性过氧化物酶体增殖物反应元件（PPRE）结合并促进IDE基因转录，在调节大鼠原代神经元中IDE表达方面发挥重要作用。最后，我们证明PPARγ参与神经元中胰岛素诱导的IDE表达。这些结果表明，PPARγ通过转录诱导IDE表达，这为在DM2和AD治疗中使用PPARγ激动剂提供了一种新机制。
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