Open AccessDifferential expression and activation of a family of murine peroxisome proliferator-activated receptors.
Author(s) -
Steven A. Kliewer,
Barry M. Forman,
Bruce Blumberg,
Estelita S. Ong,
Uwe Borgmeyer,
David J. Mangelsdorf,
Kazuhiko Umesono,
Ronald M. Evans
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.15.7355
Subject(s) - peroxisome proliferator activated receptor , peroxisome , gene isoform , peroxisome proliferator activated receptor alpha , activator (genetics) , peroxisome proliferator activated receptor delta , biology , receptor , peroxisome proliferator activated receptor gamma , peroxisome proliferator , transcription factor , nuclear receptor , biochemistry , microbiology and biotechnology , gene
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.