Document Detail


Oxazolidinones inhibit cellular proliferation via inhibition of mitochondrial protein synthesis.
MedLine Citation:
PMID:  16127068     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oxazolidinones are a relatively new structural class of antibacterial agents that act by inhibiting bacterial protein synthesis. The oxazolidinones inhibit mitochondrial protein synthesis, as shown by [35S]methionine incorporation into intact rat heart mitochondria. Treatment of K562 human erythroleukemia cells with the oxazolidinone eperezolid resulted in a time- and concentration-dependent inhibition of cell proliferation. The cells remained viable, but an increase in doubling time was observed with eperezolid treatment. Inhibition was reversible, since washing and refeeding of cells in the absence of compound resulted in a resumption of growth. The growth-inhibitory effect of the oxazolidinones did not appear to be cell type specific, and inhibition of CHO and HEK cells also was demonstrated. Treatment of cells resulted in a decrease in mitochondrial cytochrome oxidase subunit I levels, consistent with an inhibition of mitochondrial protein synthesis. Eperezolid caused no growth inhibition of rho zero (rho0) cells, which contain no mitochondrial DNA; however, the growth of the parent 143B cells was inhibited. These results provide a direct demonstration that the inhibitory effect of eperezolid in mammalian cells is the result of mitochondrial protein synthesis inhibition.
Authors:
Eva E Nagiec; Luping Wu; Steve M Swaney; John G Chosay; Daniel E Ross; Joan K Brieland; Karen L Leach
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  49     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-29     Completed Date:  2005-11-22     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3896-902     Citation Subset:  IM    
Affiliation:
Department of Antibacterial Pharmacology, Pfizer, Ann Arbor, MI 48105, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetamides / pharmacology
Animals
Blotting, Western
Cell Proliferation / drug effects*
Cells, Cultured
Flow Cytometry
Humans
K562 Cells
Mitochondria, Heart / drug effects*,  metabolism*
Oxazoles / pharmacology*
Oxazolidinones / pharmacology
Protein Synthesis Inhibitors*
Rats
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Acetamides; 0/Oxazoles; 0/Oxazolidinones; 0/Protein Synthesis Inhibitors; 165800-03-3/linezolid; C460ZSU1OW/eperezolid
Comments/Corrections

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