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

Xuerui Yang, Christina Chan

Research output: Contribution to journalArticle

  • 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
eIF-2 Kinase
Proteins
Double-Stranded RNA
JNK Mitogen-Activated Protein Kinases
Nonesterified Fatty Acids
Hepatocellular Carcinoma
Transcription Factors
Fatty Acids
Down-Regulation
Amino Acids

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: Contribution to journalArticle

@article{d062fb0568404a4eacdea84c8f1d5e01,
title = "Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2",
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.",
keywords = "Apoptosis, HepG2, JNK, NF-?B, Palmitate, Phosphorylation of Bcl-2, PKR",
author = "Xuerui Yang and Christina Chan",
year = "2009",
month = "4",
doi = "10.1038/cr.2009.25",
language = "English (US)",
volume = "19",
pages = "469--486",
journal = "Cell Research",
issn = "1001-0602",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2

AU - Yang,Xuerui

AU - Chan,Christina

PY - 2009/4

Y1 - 2009/4

N2 - 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.

AB - 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.

KW - Apoptosis

KW - HepG2

KW - JNK

KW - NF-?B

KW - Palmitate

KW - Phosphorylation of Bcl-2

KW - PKR

UR - http://www.scopus.com/inward/record.url?scp=64149098793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64149098793&partnerID=8YFLogxK

U2 - 10.1038/cr.2009.25

DO - 10.1038/cr.2009.25

M3 - Article

VL - 19

SP - 469

EP - 486

JO - Cell Research

T2 - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 4

ER -