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

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.

Protective effect of peroxisome proliferator activated receptor gamma agonists on diabetic and non‐diabetic renal diseases

“…RGTZ protects renal, myocardial and cerebral ischemia 34,45,51,52 and its antiapoptotic effect is regarded as a protective mechanism. In an in vitro study, troglitazone suppressed apoptosis of clonal tubular epithelial cells 53 . In our preliminary study, we found that RGTZ prevented CsA‐induced apoptotic death of renal tubular cell, which is a main cause of cell death in CsA‐induced renal tubular injury 54–56 .…”

Activation of Peroxisome Proliferator-Activated Receptor γ Contributes to the Survival of T Lymphoma Cells by Affecting Cellular Metabolism

“…In addition to our report, several groups have found that PPAR␥ improves cell survival in other systems. Haraguchi et al 37 reported that several PPAR␥ agonists inhibit serum starvation induced apoptosis in kidney cells. In addition, it has been shown that infusion of 15d-PGJ 2 and rosiglitazone resulted in reduction in size of brain infarct 38 as well as myocardial infarct in rats.…”

Increased expression of the lipocalin 24p3 as an apoptotic mechanism for MK886

“…In contrast, ciglitazone reduced MK886-induced cell apoptosis Figure 6). Interestingly, two recent reports [34,35] have shown that several thiazolidinedione PPARγ agonists can protect lymphocytes and LLC-PK1 cells from apoptosis.…”