Document Detail

BimEL-dependent apoptosis induced in peripheral blood lymphocytes with n-butyric acid is moderated by variation in expression of c-myc and p21(WAF1).
MedLine Citation:
PMID:  18348176     Owner:  NLM     Status:  MEDLINE    
We have examined the effect of sodium butyrate (SB) on the viability of normal peripheral blood lymphocytes (PBLs) in vitro and the effect of this agent on the expression of 20 apoptosis-related genes. Data suggest that PBL treated with 2 mmol L(-1) SB resisted for at least 8 h the destructive activity of the agent, but eventually 30% of cells died within 72 h. As documented by flow cytometry and cytochrome c release study, cells underwent mitochondrial-derived apoptosis. While the expression of the majority of genes examined by RT-PCR and Western blots remained indifferent to 2 mmol L(-1) SB, the cellular levels of BimEL, c-myc, p53, and p21(WAF1) varied profoundly with the time of SB treatment. The Bax activator BimEL increased rapidly, driving cells toward apoptosis likely controlled by c-myc and p21(WAF1) activities. The c-myc, exercising the role of mediator of the function of BimEL and inhibitor of p21(WAF1) expression, decreased significantly for several hours after adding SB but within 48 h it returned to close to its original value. An apoptosis inhibitor and executive caspase substrate p21(WAF1) increased early at the beginning of treatment but subsequently, within a time frame of 72 h, profoundly dropped in terms of both a caspase-dependent and caspase-independent way. We suggest that variations in c-myc and p21(WAF1) expression delay apoptosis making PBL resistant to SB for several hours, and together with fast catabolism of SB in vivo protect PBL against the destructive activity of this anti-cancerous metabolite of colonic bacteria.
Ivan Kalousek; Barbora Brodska; Petra Otevrelova; Pavla Röselova
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell biochemistry and function     Volume:  26     ISSN:  1099-0844     ISO Abbreviation:  Cell Biochem. Funct.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-29     Completed Date:  2008-08-12     Revised Date:  2008-10-02    
Medline Journal Info:
Nlm Unique ID:  8305874     Medline TA:  Cell Biochem Funct     Country:  England    
Other Details:
Languages:  eng     Pagination:  509-21     Citation Subset:  IM    
Copyright Information:
(c) 2008 John Wiley & Sons, Ltd.
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
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MeSH Terms
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / genetics,  metabolism*
Butyric Acid / pharmacology*
Caspases / metabolism
Cells, Cultured
Collagen Type XI / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism*
Cytochromes c / metabolism,  secretion
Enzyme Activation
Gene Expression Regulation / drug effects
Intracellular Membranes / drug effects
Lymphocytes / drug effects*,  metabolism*,  secretion
Membrane Proteins / genetics,  metabolism*
Mitochondria / drug effects
Proto-Oncogene Proteins / genetics,  metabolism*
Proto-Oncogene Proteins c-myc / genetics,  metabolism*
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/CDKN1A protein, human; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/MYC protein, human; 0/Membrane Proteins; 0/Perp protein, mouse; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myc; 0/Reactive Oxygen Species; 107-92-6/Butyric Acid; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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