Dedifferentiated hepatoma cells, in contrast to most other cell types including hepatoma cells, undergo apoptosis when treated with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the dedifferentiated hepatoma cells also exhibit a strong and prolonged NF-κB induction phenotype upon exposure to LPS, suggesting that NF-κB signaling may play a pro-survival role, as reported in several other cell systems. To test the role of NF-κB in preventing LPS-mediated apoptosis, we examined the dedifferentiated cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated cell death in the M38 cells, yet only modestly inhibited NF-κB induction. In addition, inhibition of NF-κB translocation by infection of the M38 cells with an adenoviral vector expressing an IκBα super-repressor did not result in LPS-mediated cell death. These results suggest that unlike TNFα induction, the cell survival pathway activated in response to LPS is independent of NF-κB translocation in the dedifferentiated cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, cell survival pathways other than those involving NF-κB inducible gene expression or other well-known pathways appear to be involved in protecting the dedifferentiated hepatoma variant cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function of loss of hepatic gene expression, as the parental hepatoma cells resist LPS-mediated apoptosis in the presence of protein synthesis inhibitors.
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Research Article|
August 06 2007
Apoptosis of Dedifferentiated Hepatoma Cells is Independent of NF-κB Activation in Response to LPS
M. Ryan Reidy;
M. Ryan Reidy
1Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
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Janette Ellis;
Janette Ellis
1Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
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Erin A. Schmitz;
Erin A. Schmitz
1Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
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David M. Kraus;
David M. Kraus
1Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
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Gary A. Bulla
Gary A. Bulla
1Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
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Publisher: Portland Press Ltd
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 2007 The Biochemical Society
2007
Biosci Rep (2007) 27 (4-5): 235–246.
Citation
M. Ryan Reidy, Janette Ellis, Erin A. Schmitz, David M. Kraus, Gary A. Bulla; Apoptosis of Dedifferentiated Hepatoma Cells is Independent of NF-κB Activation in Response to LPS. Biosci Rep 6 August 2007; 27 (4-5): 235–246. doi: https://doi.org/10.1007/s10540-007-9049-9
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