Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2

Xuerui Yang, Christina Chan

    Research output: Research - peer-reviewArticle

    • 25 Citations

    Abstract

    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-B 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.

    LanguageEnglish (US)
    Pages469-486
    Number of pages18
    JournalCell Research
    Volume19
    Issue number4
    DOIs
    StatePublished - Apr 2009

    Profile

    Palmitates
    Hep G2 Cells
    Phosphorylation
    Apoptosis
    Proteins
    eIF-2 Kinase
    Double-Stranded RNA
    JNK Mitogen-Activated Protein Kinases
    Nonesterified Fatty Acids
    Hepatocellular Carcinoma
    Transcription Factors
    Fatty Acids
    Down-Regulation
    Amino Acids
    3'-(1-butylphosphoryl)adenosine

    Keywords

    • Apoptosis
    • HepG2
    • JNK
    • NF-?B
    • Palmitate
    • Phosphorylation of Bcl-2
    • PKR

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology

    Cite this

    Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2. / Yang, Xuerui; Chan, Christina.

    In: Cell Research, Vol. 19, No. 4, 04.2009, p. 469-486.

    Research output: Research - peer-reviewArticle

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