The present study shows that
double-stranded RNA-dependent
protein kinase (PKR) regulates the
protein expression level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human
hepatocellular carcinoma cells (HepG2). In various types of cells, saturated
free fatty acids (FFAs), such as
palmitate, have been shown to induce cellular apoptosis by several mechanisms.
Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2
protein, mediated in part by reduced activation of the
NF-kappaB transcription factor. In addition to the level of Bcl-2
protein, 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 inhibition of PKR and possibly by
c-Jun N-terminal kinase (JNK), whereas the phosphorylation of Bcl-2 at Ser87 is unaffected 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.