一组小鼠过氧化物酶体增殖物激活受体的差异表达与激活

Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.

作者信息

Kliewer S A, Forman B M, Blumberg B, Ong E S, Borgmeyer U, Mangelsdorf D J, Umesono K, Evans R M

机构信息

Salk Institute for Biological Studies, La Jolla, CA.

出版信息

Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9. doi: 10.1073/pnas.91.15.7355.

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms.

为深入了解过氧化物酶体增殖物激活受体（PPAR）亚型在哺乳动物中的功能，我们从小鼠中克隆并鉴定了两个与PPARα相关的cDNA（分别命名为PPARγ和 -δ）。这三种PPAR亚型在胚胎发育过程中和成年期表现出广泛不同的表达模式。令人惊讶的是，PPARγ和 -δ不会被强力过氧化物酶体增殖剂和PPARα激活剂吡格列酸（Wy 14,643）激活。然而，PPARγ和 -δ分别被结构不同的过氧化物酶体增殖剂LY - 171883和亚油酸激活，这表明每种亚型都可以作为转录的调节激活剂。这些数据表明，包括某些脂肪酸在内的组织对过氧化物酶体增殖剂的特异性反应，部分是多种药理学上不同的PPAR亚型差异表达的结果。