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Albumin Regulates Induction of Peroxisome Proliferator-Activated Receptor- (PPAR) by 15-Deoxy-^12–14-Prostaglandin J₂ in Vitro and May Be an Important Regulator of PPAR Function in Vivo¹

Graduate Group in Biophysics (E.C.P.), Departments of Pharmaceutical Chemistry (T.S.S.), Cellular and Molecular Pharmacology (T.S.S.), and Obstetrics, Gynecology, and Reproductive Sciences (L.L.W., R.N.T.), University of California, San Francisco, California 94143

Address all correspondence and requests for reprints to: Dr. Thomas S. Scanlan, Department of Pharmaceutical Chemistry, University of California, Box 0446, San Francisco, California 94143-0446. E-mail: scanlan{at}cgl.ucsf.edu

We observed that serum contains a factor(s) that inhibits the induction of peroxisome proliferator-activated receptor- (PPAR) by 15-deoxy-^12,14-PGJ₂ (15dJ₂). Ten percent FBS reduces 15dJ₂ induction of PPAR from over 150-fold to less than 15-fold in EP-JEG cells, a stably transfected choriocarcinoma cell line that expresses endogenous PPAR. By contrast, rosiglitazone, an unrelated pharmacological agonist of PPAR, is not inhibited by serum in this cell line. We have identified the inhibitory principal in serum as albumin. Serum albumin binds 15dJ₂ with a dissociation constant of 870 ± 70 nM, effectively reducing the concentration of 15dJ₂ available to PPAR. 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 15dJ₂ or structurally similar compounds or metabolites are the endogenous activators of PPAR. Therefore, albumin may be an important regulator of PPAR function in vivo.

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