Variations in c-Myc and p21WAF1 expression protect normal peripheral blood lymphocytes against BimEL-mediated cell death
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19330811
DOI
10.1002/cbf.1552
Knihovny.cz E-resources
- MeSH
- Enzyme Activation drug effects MeSH
- Cell Membrane drug effects metabolism MeSH
- Cell Death drug effects MeSH
- Cytochromes c metabolism MeSH
- Cytoprotection * drug effects MeSH
- Phosphatidylserines metabolism MeSH
- Cyclin-Dependent Kinase Inhibitor p21 metabolism MeSH
- Caspases metabolism MeSH
- Hydroxamic Acids pharmacology MeSH
- Humans MeSH
- Lymphocytes cytology drug effects enzymology metabolism MeSH
- Membrane Proteins metabolism MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Mitochondria drug effects metabolism MeSH
- Poly(ADP-ribose) Polymerases metabolism MeSH
- Bcl-2-Like Protein 11 MeSH
- Apoptosis Regulatory Proteins metabolism MeSH
- Proto-Oncogene Proteins c-myc metabolism MeSH
- Proto-Oncogene Proteins metabolism MeSH
- Reactive Oxygen Species metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Protein Transport drug effects MeSH
- Cell Survival drug effects MeSH
- Vorinostat MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- BCL2L11 protein, human MeSH Browser
- Cytochromes c MeSH
- Phosphatidylserines MeSH
- Cyclin-Dependent Kinase Inhibitor p21 MeSH
- Caspases MeSH
- Hydroxamic Acids MeSH
- Membrane Proteins MeSH
- Poly(ADP-ribose) Polymerases MeSH
- Bcl-2-Like Protein 11 MeSH
- Apoptosis Regulatory Proteins MeSH
- Proto-Oncogene Proteins c-myc MeSH
- Proto-Oncogene Proteins MeSH
- Reactive Oxygen Species MeSH
- Vorinostat MeSH
We have examined the effect of suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) on the viability of normal peripheral blood lymphocytes (PBLs) in vitro and on the expression of 20 apoptosis-related genes. RT-PCR, western blots and flow cytometry were performed to reveal the proteins of apoptosis machinery that were affected to cause cell death. Our data suggest that PBL markedly resisted for approximately 24 h the destructive activity of the agent, but eventually 60% of cells treated with 4 micromol/L SAHA died within 72 h through mitochondrial way of apoptosis. While the expression of the majority of genes remained indifferent against 4 micromol/L SAHA, the cellular levels of BimEL, Bmf-2, Bcl-w and survivin mRNA varied, confirming the pro-apoptotic response of SAHA treated PBL. In addition, the expression of multifunctional proteins c-Myc and p21(WAF1) changed profoundly with the time of SAHA treatment. The Bax activator BimEL increased rapidly, driving cells towards apoptosis likely controlled by c-Myc and p21(WAF1) activities. We suggest that variations in c-Myc and p21(WAF1) expression decelerate the apoptosis in the early period and increase the resistance of resting PBL against SAHA.
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