Differential Expression and Activation of a Family of Murine Peroxisome Proliferator-Activated Receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 15; pp. 7355 - 7359
• Main Authors: Kliewer, S. A., Forman, B. M., Blumberg, B., Ong, E. S., Borgmeyer, U., Mangelsdorf, D. J., Umesono, K., Evans, R. M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 19.07.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Acetophenones - pharmacology; Aging - metabolism; Amino Acid Sequence; Anatomy & physiology; Animals; Base Sequence; Blotting, Northern; Cloning, Molecular; DNA; Embryo, Mammalian - metabolism; Fatty acids; Genes; Genetic screening; Linoleic Acid; Linoleic Acids - pharmacology; Mice; Molecular Sequence Data; Peroxisome proliferators; Peroxisomes; Pharmacology; Physiology; Plasmids; Protein isoforms; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; RNA; Rodents; Tetrazoles - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0027-8424; 1091-6490
• 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 PPARα-related cDNAs (designated PPARγ and -δ, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPARγ and -δ are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPARα. However, PPARγ and -δ 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.