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

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.