PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

被引：66

作者：

Du, Jing ^{[1
]}

Zhang, Lang ^{[1
]}

Liu, Shubo ^{[1
]}

Zhang, Chi ^{[1
]}

Huang, Xiuqing ^{[2
,3
]}

Li, Jian ^{[2
,3
]}

Zhao, Naming ^{[1
]}

Wang, Zhao ^{[1
]}

机构：

[1] Tsinghua Univ, Prot Sci Key Lab, Minist Educ, Dept Biol Sci & Biotechnol,Sch Med, Beijing 100084, Peoples R China

[2] Beijing Hosp, Key Lab Geriatr, Beijing 100730, Peoples R China

[3] Beijing Inst Geriatr, Minist Hlth, Beijing 100730, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 383卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Insulin-degrading enzyme; Peroxisome proliferator-activated receptor gamma; Type 2 diabetes mellitus; Alzheimer's disease; Transcriptional regulation; ACTIVATED-RECEPTOR-GAMMA; ONSET ALZHEIMERS-DISEASE; DIABETES SUSCEPTIBILITY; GENE; ASSOCIATION; DEGRADATION; MICE; CANDIDATE; SEQUENCE; LINKAGE;

D O I：

10.1016/j.bbrc.2009.04.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a key role in degrading both A beta 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 (PPAR gamma) levels. Further studies show that PPAR gamma 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 PPAR gamma participates in the insulin-induced IDE expression in neurons. These results suggest that PPAR gamma transcriptionally induces IDE expression which provides a novel mechanism for the use of PPAR gamma agonists in both DM2 and AD therapies. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：485 / 490

页数：6

共 23 条

[1] Ligand-independent activation of peroxisome proliferator-activated receptor-γ by insulin and C-peptide in kidney proximal tubular cells -: Dependent on phosphatidylinositol 3-kinase activity [J].