We observed that serum contains a factor(s) that inhibits the induction of peroxisome proliferator-activated receptor-γ (PPARγ) by 15-deoxy-Δ12,14-PGJ2 (15dJ2). Ten percent FBS reduces 15dJ2 induction of PPARγ from over 150-fold to less than 15-fold in EP-JEG cells, a stably transfected choriocarcinoma cell line that expresses endogenous PPARγ. By contrast, rosiglitazone, an unrelated pharmacological agonist of PPARγ, 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 PPARγ. 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 PPARγ. Therefore, albumin may be an important regulator of PPARγ function in vivo.
ASJC Scopus subject areas