Synthesis of ABCA1 protein in liver is necessary for high-density lipoproteins (HDL) formation in mammals Nuclear receptor PPAR gamma is known as activator of ABCA1 expression, but details of PPAR gamma-mediated regulation of ABCA1 at both transcriptional and post-transcriptional levels in hepatocytes have not still been well elucidated. In this study we have shown, that PPAR gamma activates ABCA1 gene transcription in human hepatoma cells HepG2 through increasing of LXR beta binding with promoter region of ABCA1 gene Treatment of HepG2 cells with PPAR gamma agonist GW1929 leads to dissociation of LXR beta from ABCA1/LXR beta complex and to nuclear translocation of this nuclear receptor resulting in reduction of ABCA1 protein level 24 h after treatment. Inhibition of protein kinases MEK1/2 abolishes PPAR gamma-mediated dissociation of LXR beta from ABCA1/LXR beta complex, but does not block PPAR gamma-dependent clown-regulation of ABCA1 protein in HepG2 cells These data suggest that PPAR gamma may be important for regulation of the level of hepatic ABCA1 protein and indicate the new interplays between PPAR gamma, LXR beta and MEK1/2 in regulation of ABCA1 mRNA and protein expression (C) 2010 Elsevier Inc All rights reserved