Two Synthetic Ligands for Peroxisome Proliferator-Activated Receptor γ

저작시기 2004.06 |등록일 2009.04.22 파일확장자어도비 PDF (pdf) | 6페이지 | 가격 6,000원
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서지정보

발행기관 : 대한의생명과학회 수록지정보 : 대한의생명과학회지 / 10권 / 2호
저자명 : Mina Kim, Sunhyo Jeong, Yang-Heon Song, Dae-Il Kim, Michung Yoon

목차

영어 초록
INTRODUCTION
METHODS
RESULTS
DISCUSSION
Acknowledgements
REFERENCES

한국어 초록

The peroxisome proliferator-activated receptor γ (PPARγ) is the molecular target for a class of drugs, the antidiabetic thiazolidnediones (TZDs). The heterodimer of PPARγ with retinoid X receptor (RXR) plays a central role in the regulation of adipogenesis and insulin sensitization. We synthesized two chemicals, DANA87 and DANA88, sharing structural characteristics with TZDs. Given this structural similarity, it was hypothesized that DANA87 and DANA88 may act as PPARγ ligands. In transient transfection assays, DANA87 and DANA88 caused slight increases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element in 3T3-L1 preadipocytes. However, DANA87 and DANA88 significantly inhibited troglitazone-induced reporter gene activation when cells were treated with a combination of DANA87 or DANA 88 and troglitazone, one of the TZDs that activate PPARγ. These results suggest that DANA87 and DANA88 are not only weak agonists of PPARγ transactivation, but also competitively antagonize troglitazone-induced PPARγ reporter activity.

영어 초록

The peroxisome proliferator-activated receptor γ (PPARγ) is the molecular target for a class of drugs, the antidiabetic thiazolidnediones (TZDs). The heterodimer of PPARγ with retinoid X receptor (RXR) plays a central role in the regulation of adipogenesis and insulin sensitization. We synthesized two chemicals, DANA87 and DANA88, sharing structural characteristics with TZDs. Given this structural similarity, it was hypothesized that DANA87 and DANA88 may act as PPARγ ligands. In transient transfection assays, DANA87 and DANA88 caused slight increases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element in 3T3-L1 preadipocytes. However, DANA87 and DANA88 significantly inhibited troglitazone-induced reporter gene activation when cells were treated with a combination of DANA87 or DANA 88 and troglitazone, one of the TZDs that activate PPARγ. These results suggest that DANA87 and DANA88 are not only weak agonists of PPARγ transactivation, but also competitively antagonize troglitazone-induced PPARγ reporter activity.

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