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Regulation of Cellular Apoptosis by Palmitic Acid and TNF‐alpha: Involvement of Signal Transduction Pathways from PKR to Bcl‐2
Author(s) -
Yang Xuerui,
Chan Christina
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1346-d
Subject(s) - protein kinase r , apoptosis , phosphorylation , signal transduction , microbiology and biotechnology , tumor necrosis factor alpha , palmitic acid , kinase , eif 2 kinase , biology , chemistry , protein kinase a , endocrinology , biochemistry , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , fatty acid
Saturated FFAs (e.g. palmitate) induced apoptosis is associated with the development of a variety of diseases. Palmitate has been shown to induce apoptosis in liver cells by decreasing the protein level of Bcl‐2, however, the intermediates that mediate this affect are not known. In the present study we identified that the palmitate‐induced apoptosis through Bcl‐2 is mediated by double‐stranded RNA‐dependent protein kinase (PKR) . We identified for the first time that palmitate and TNF‐α down‐regulated the activity of PKR, which is required to maintain the level of Bcl‐2 in HepG2 cells. We propose that the transcription factor, NF‐κB, is involved in mediating the effect of PKR on the Bcl‐2 level. In addition, we showed a decrease in the phosphorylation of Bcl‐2 at Ser70, which was mediated by PKR and JNK, while the phosphorylation of Bcl‐2 at Ser87 was not affected upon exposure to palmitate and TNF‐α. Furthermore, we show that eIF‐2α and PP2A, the most well‐known substrates of PKR, are not involved in mediating the apoptosis induced by palmitate and TNF‐α. In summary, we identified the signaling pathways that are activated upon exposure to palmitate and regulate the protein level and the phosphorylation status of the Bcl‐2 protein and therefore apoptosis in HepG2 cells.