Signals That Regulate Astroglial Gene Expression: Induction of GFAP mRNA Following Seizures or Injury Is Blocked by Protein Synthesis Inhibitors

1997 ◽  
Vol 148 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Oswald Steward ◽  
Melinda S. Kelley ◽  
P.Elyse Schauwecker
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Protein Synthesis Inhibitors

scholarly journals Abundance of hepatic metallothionein mRNA is increased by protein-synthesis inhibitors. Evidence for transcriptional activation and post-transcriptional regulation

1991 ◽  
Vol 273 (1) ◽  
pp. 185-188 ◽  
Author(s):  
C C McCormick ◽  
L M Salati ◽  
A G Goodridge
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Transcriptional Regulation ◽  
Transcriptional Activation ◽  
Actinomycin D ◽  
Protein Synthesis Inhibitors ◽  
Mrna Accumulation ◽  
Hepatic Metallothionein ◽  
Post Transcriptional Regulation

Ongoing protein synthesis is a prerequisite in the expression of some genes. We studied the effect of various protein synthesis inhibitors on the expression of the avian metallothionein (MT) gene. Chicken embryonic hepatocytes in culture were exposed to various concentrations of cycloheximide, puromycin and pactamycin. At concentrations which decreased total protein synthesis by about 90% each inhibitor increased MT mRNA accumulation approx. 5-fold at 9 h of incubation. Incubation with puromycin or zinc for 2 h markedly increased the rate of MT gene transcription. Estimates of the half-life of MT mRNA by using actinomycin D suggested for cycloheximide, but not puromycin, decreased the decay rate of MT mRNA. These data suggest the potential for post-transcriptional regulation of the avian MT gene. We conclude that different antibiotics increase the accumulation of hepatocyte MT mRNA by different mechanisms and that the possibility of multiple mechanisms should be considered in other studies of the role of protein synthesis in gene expression.

Apoptosis of Dedifferentiated Hepatoma Cells is Independent of NF-κB Activation in Response to LPS

2007 ◽  
Vol 27 (4-5) ◽  
pp. 235-246
Author(s):  
M. Ryan Reidy ◽  
Janette Ellis ◽  
Erin A. Schmitz ◽  
David M. Kraus ◽  
Gary A. Bulla
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Protein Synthesis ◽  
Cell Survival ◽  
Cell Types ◽  
Hepatoma Cells ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibitor ◽  
Dedifferentiated Hepatoma

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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