Activation of Peroxisome Proliferator-Activated Receptor-g Inhibits Apoptosis Induced by Serum Deprivation in LLC-PK1 Cells

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Abstract
Peroxisome proliferator-activated receptor-γ (PPARγ) belongs to a superfamily of nuclear receptors, which plays important roles in lipid and glucose metabolism. However, expression of PPARγ in extra-adipose tissues and stimulation of apoptosis by PPARγ activators has been previously reported. We investigated the functions of PPARγ using a clonal kidney cell line (LLC-PK1). RT-PCR revealed the expression of PPARγ in LLC-PK1 cells. The cells accumulated fat droplets and increased β-oxidation of free fatty acids in response to troglitazone, a ligand for PPARγ. At physiological concentrations, ligands for PPARγ including troglitazone, BRL49653, and 15-deoxy-δ-12,14-prostaglandin J2 inhibited serum-deprivation-induced apoptosis of the cells. On the other hand, PPARα activators did not inhibit the apoptosis. Apoptosis of LLC-PK1 cells was determined by a cell viability assay, condensation of the nucleus on fluorescent and electron microscopy, and DNA fragmentation as indicated by the appearance of nucleosomal ladders on an agarose gel. Troglitazone also suppressed serum-deprivation-induced activation of Caspase 3. However, troglitazone did not suppress apoptosis induced by ATP deprivation. Anti-apoptotic effects of troglitazone were partially blocked by a phosphatidylinositol-3-kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors such as PD98059 and AG490. These results suggest that PPARγ is functionally expressed in LLC-PK1 cells, and its activation inhibits apoptosis induced by serum deprivation, at least in part, through the PI3K pathway.