Repression of PKR Mediates Palmitate-Induced Apoptosis in

In the present study we found that double-stranded RNA-dependent protein kinase (PKR) regulates the protein expression level and the phosphorylation of Bcl-2 and exploits an anti-apoptotic role in human hepatocellular carcinoma cells (HepG2). Saturated free fatty acids (FFAs), e.g. palmitate, have been shown to induce cellular apoptosis in various types of cells by different mechanisms. We found palmitate down-regulates the activity of PKR, and thereby decreases the protein level of Bcl-2, mediated, in part, by the NF-κB transcription factor. In addition to the protein level of Bcl-2, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylation of Bcl-2 at Ser70 upon exposure to palmitate is mediated by PKR and possibly JNK, while the phosphorylation of Bcl-2 at Ser87 is not affected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bcl-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells