Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
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.
Kliewer
S A
SA
Salk Institute for Biological Studies, La Jolla, CA.
Forman
B M
BM
Blumberg
B
B
Ong
E S
ES
Borgmeyer
U
U
Mangelsdorf
D J
DJ
Umesono
K
K
Evans
R M
RM
D000098:Acetophenones / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA; D004622:Embryo, Mammalian / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000098:Acetophenones; D008041:Linoleic Acids; D018160:Receptors, Cytoplasmic and Nuclear; D013777:Tetrazoles; D014157:Transcription Factors; C044660:LY 171883; D004247:DNA; D019787:Linoleic Acid