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
相关论文
共 27 条
  • [1] THE NEURONAL MINERALOCORTICOID RECEPTOR AS A MEDIATOR OF GLUCOCORTICOID RESPONSE
    ARRIZA, JL
    SIMERLY, RB
    SWANSON, LW
    EVANS, RM
    [J]. NEURON, 1988, 1 (09) : 887 - 900
  • [2] PPAR-RXR HETERODIMER ACTIVATES A PEROXISOME PROLIFERATOR RESPONSE ELEMENT UPSTREAM OF THE BIFUNCTIONAL ENZYME GENE
    BARDOT, O
    ALDRIDGE, TC
    LATRUFFE, N
    GREEN, S
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 192 (01) : 37 - 45
  • [3] THE ONTOGENY OF PEROXISOME-PROLIFERATOR-ACTIVATED RECEPTOR GENE-EXPRESSION IN THE MOUSE AND RAT
    BECK, F
    PLUMMER, S
    SENIOR, PV
    BYRNE, S
    GREEN, S
    BRAMMAR, WJ
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1992, 247 (1319) : 83 - 87
  • [4] BLACK VH, 1980, AM J ANAT, V159, P85, DOI 10.1002/aja.1001590108
  • [5] MULTIPLE RETINOID-RESPONSIVE RECEPTORS IN A SINGLE CELL - FAMILIES OF RETINOID X RECEPTORS AND RETINOIC ACID RECEPTORS IN THE XENOPUS EGG
    BLUMBERG, B
    MANGELSDORF, DJ
    DYCK, JA
    BITTNER, DA
    EVANS, RM
    DEROBERTIS, EM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (06) : 2321 - 2325
  • [6] IDENTIFICATION OF 2 MESSENGER PPAR RELATED RECEPTORS AND EVIDENCE FOR THE EXISTENCE OF 5 SUBFAMILY MEMBERS
    CHEN, F
    LAW, SW
    OMALLEY, BW
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 196 (02) : 671 - 677
  • [7] CONTROL OF THE PEROXISOMAL BETA-OXIDATION PATHWAY BY A NOVEL FAMILY OF NUCLEAR HORMONE RECEPTORS
    DREYER, C
    KREY, G
    KELLER, H
    GIVEL, F
    HELFTENBEIN, G
    WAHLI, W
    [J]. CELL, 1992, 68 (05) : 879 - 887
  • [8] EFFECT OF THE PEROXISOME PROLIFERATOR LY171883 ON TRIGLYCERIDE ACCUMULATION IN RATS FED A FAT-FREE DIET
    FOXWORTHY, PS
    EACHO, PI
    [J]. BIOCHEMICAL PHARMACOLOGY, 1991, 42 (07) : 1487 - 1491
  • [9] INTERACTION OF THE PEROXISOME-PROLIFERATOR-ACTIVATED RECEPTOR AND RETINOID X-RECEPTOR
    GEARING, KL
    GOTTLICHER, M
    TEBOUL, M
    WIDMARK, E
    GUSTAFSSON, JA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (04) : 1440 - 1444
  • [10] FATTY-ACIDS ACTIVATE A CHIMERA OF THE CLOFIBRIC ACID-ACTIVATED RECEPTOR AND THE GLUCOCORTICOID RECEPTOR
    GOTTLICHER, M
    WIDMARK, E
    LI, Q
    GUSTAFSSON, JA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) : 4653 - 4657