Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone

被引：271

作者：

Sakamoto, J

Kimura, H

Moriyama, S

Odaka, H

Momose, Y

Sugiyama, Y

Sawada, H

机构：

[1] Takeda Chem Ind Ltd, Pharmaceut Discovery Res Div, Discovery Res Labs 4, Yodogawa Ku, Osaka 5328686, Japan

[2] Takeda Chem Ind Ltd, Pharmaceut Res Labs 2, Osaka 5328686, Japan

[3] Takeda Chem Ind Ltd, Med Chem Res Labs, Div Pharmaceut Res, Osaka 5328686, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2000年 / 278卷 / 03期

关键词：

pioglitazone; thiazolidinedione; PPAR; transactivation assay; binding assay; apoA-I;

D O I：

10.1006/bbrc.2000.3868

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：

Pioglitazone, a thiazolidinedione (TZD) derivative, is an antidiabetic agent that improves hyperglycaemia and hyperlipidaemia in obese and diabetic animals via a reduction in hepatic and peripheral insulin resistance. The TZDs including pioglitazone have been identified as high affinity ligands for peroxisome proliferator-activated receptor (PPAR) gamma. The selectivity of pioglitazone for the human PPAR subtypes has not been reported, thus, we investigated the effect of pioglitazone on the human PPAR subtypes. Transient transactivation assay showed that pioglitazone is a selective hPPAR gamma1 activator and a weak hPPAR alpha activator. Binding assay indicated that the transactivation of hPPAR gamma1 or hPPAR alpha by pioglitazone is due to direct binding of pioglitazone to each subtype. Furthermore, pioglitazone significantly increased the apoA-I secretion from the human hepatoma cell line HepG2. (C) 2000 Academic Press.

引用

页码：704 / 711

页数：8

共 28 条

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