DIFFERENTIAL EXPRESSION AND ACTIVATION OF A FAMILY OF MURINE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS

被引:1242
作者
KLIEWER, SA [1 ]
FORMAN, BM [1 ]
BLUMBERG, B [1 ]
ONG, ES [1 ]
BORGMEYER, U [1 ]
MANGELSDORF, DJ [1 ]
UMESONO, K [1 ]
EVANS, RM [1 ]
机构
[1] HOWARD HUGHES MED INST,LA JOLLA,CA 92037
关键词
NUCLEAR HORMONE RECEPTORS; FATTY ACID; BETA-OXIDATION;
D O I
10.1073/pnas.91.15.7355
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7355 / 7359
页数:5
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