Albumin regulates induction of peroxisome proliferator-activated receptor-γ (PPARγ) by 15-deoxy-Δ12-14-prostaglandin J2 in vitro and may be an important regulator of PPARγ function in vivo

被引：15
作者：
Person, EC
Waite, LL
Taylor, RN
Scanlan, TS
机构：
[1] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
来源：
ENDOCRINOLOGY | 2001年 / 142卷 / 02期
关键词：
D O I：
10.1210/en.142.2.551
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
We observed that serum contains a factor(s) that inhibits the induction of peroxisome proliferator-activated receptor-gamma (PPAR gamma) by 15-deoxy-Delta (12,14)-PGJ(2) (15dJ(2)). Ten percent FBS reduces 15dJ(2) induction of PPAR gamma from over 150-fold to less than 15-fold in EP-JEG cells, a stably transfected choriocarcinoma cell Line that expresses endogenous PPAR gamma. By contrast, rosiglitazone, an unrelated pharmacological agonist of PPAR gamma, is not inhibited by serum in this cell line. We have identified the inhibitory principal in serum as albumin. Serum albumin binds 15d(2) with a dissociation constant of 870 +/- 70 nM, effectively reducing the concentration of 15dJ(2) available to PPAR gamma. Heat treatment of serum abolishes the inhibition, providing a way to test eicosanoid compounds independently of albumin's inhibitory effect. It is reasonable to assume that 15dJ(2) or structurally similar compounds or metabolites are the endogenous activators of PPAR gamma. Therefore, albumin may be an important regulator of PPAR gamma function in vivo.
引用
收藏
页码：551 / 556
页数：6
相关论文
共 41 条
[11]   ALBUMIN-LIPID INTERACTIONS - PROSTAGLANDIN STABILITY AS A PROBE FOR CHARACTERIZING BINDING-SITES ON VERTEBRATE ALBUMINS [J].
FITZPATRICK, FA ;
WYNALDA, MA .
BIOCHEMISTRY, 1981, 20 (21) :6129-6134
[12]  
FITZPATRICK FA, 1984, J BIOL CHEM, V259, P2722
[13]  
FITZPATRICK FA, 1983, J BIOL CHEM, V258, P1713
[14]   15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA [J].
FORMAN, BM ;
TONTONOZ, P ;
CHEN, J ;
BRUN, RP ;
SPIEGELMAN, BM ;
EVANS, RM .
CELL, 1995, 83 (05) :803-812
[15]   Inducible cyclooxygenase may have anti-inflammatory properties [J].
Gilroy, DW ;
Colville-Nash, PR ;
Willis, D ;
Chivers, J ;
Paul-Clark, MJ ;
Willoughby, DA .
NATURE MEDICINE, 1999, 5 (06) :698-701
[16]  
Goldman L., 2000, CECIL TXB MED
[17]   Interleukin-4-dependent production of PPAR-γ ligands in macrophages by 12/15-lipoxygenase [J].
Huang, JT ;
Welch, JS ;
Ricote, M ;
Binder, CJ ;
Willson, TM ;
Kelly, C ;
Witztum, JL ;
Funk, CD ;
Conrad, D ;
Glass, CK .
NATURE, 1999, 400 (6742) :378-382
[18]   15-deoxy-Δ12,14-prostalandin J2, a ligand for peroxisome proliferator-activated receptor-γ, induces apoptosis in JEG3 choriocarcinoma cells [J].
Keelan, JA ;
Sato, TA ;
Marvin, KW ;
Lander, J ;
Gilmour, RS ;
Mitchell, MD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 262 (03) :579-585
[19]   9-DEOXY-DELTA-9,DELTA-12-13,14-DIHYDROPROSTAGLANDIN-D2, A METABOLITE OF PROSTAGLANDIN-D2 FORMED IN HUMAN-PLASMA [J].
KIKAWA, Y ;
NARUMIYA, S ;
FUKUSHIMA, M ;
WAKATSUKA, H ;
HAYAISHI, O .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (05) :1317-1321
[20]   Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma [J].
Kliewer, SA ;
Sundseth, SS ;
Jones, SA ;
Brown, PJ ;
Wisely, GB ;
Koble, CS ;
Devchand, P ;
Wahli, W ;
Willson, TM ;
Lenhard, JM ;
Lehmann, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4318-4323
12345