Albumin regulates induction of peroxisome proliferator-activated receptor-gamma (PPARgamma) by 15-deoxy-delta(12-14)-prostaglandin J(2) in vitro and may be an important regulator of PPARgamma function in vivo.
We observed that serum contains a factor(s) that inhibits the induction of peroxisome proliferator-activated receptor-gamma (PPARgamma) by 15-deoxy-Delta(12,14)-PGJ(2) (15dJ(2)). Ten percent FBS reduces 15dJ(2) induction of PPARgamma from over 150-fold to less than 15-fold in EP-JEG cells, a stably transfected choriocarcinoma cell line that expresses endogenous PPARgamma. By contrast, rosiglitazone, an unrelated pharmacological agonist of PPARgamma, is not inhibited by serum in this cell line. We have identified the inhibitory principal in serum as albumin. Serum albumin binds 15dJ(2) with a dissociation constant of 870 +/- 70 nM, effectively reducing the concentration of 15dJ(2) available to PPARgamma. 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 PPARgamma. Therefore, albumin may be an important regulator of PPARgamma function in vivo.
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Graduate Group in Biophysics, University of California, San Francisco, California 94143, USA.
Waite
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Taylor
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Scanlan
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D006358:Hot Temperature; D007155:Immunologic Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D000077154:Rosiglitazone; D012709:Serum Albumin / Q000378:metabolism / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D018160:Receptors, Cytoplasmic and Nuclear; D012709:Serum Albumin; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D015230:Prostaglandin D2