PPAR{gamma} transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

Journal Article · Fri Jun 12 00:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.04.047· OSTI ID:22199718

Du, Jing; Zhang, Lang; Liu, Shubo; Zhang, Chi ^[1]; Huang, Xiuqing; Li, Jian ^[2]; Zhao, Nanming ^[1]; Wang, Zhao ^[1]

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1. Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084 (China)
2. The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730 (China)

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.

• OSTI ID: 22199718
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 383, Issue 4; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DIABETES MELLITUS
ENZYMES
GENE REGULATION
INSULIN
NERVE CELLS
NERVOUS SYSTEM DISEASES
PATHOLOGY
PATIENTS
PROMOTERS
RATS
RECEPTORS
TRANSCRIPTION