Document Detail


Modeling suppression of cell death by Bcl-2 over-expression in myeloma NS0 6A1 cells.
MedLine Citation:
PMID:  16988783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel population-balance model was employed to evaluate the suppression of cell death in myeloma NS0 6A1 cells metabolically engineered to over-express the apoptotic suppressor Bcl-2. The model is robust in its ability to simulate cell population dynamics in batch suspension culture and in response to thymidine-induced growth inhibition: 89% of simulated cell concentrations are within two standard deviations of experimental data. Kinetic rate constants in model equations suggest that Bcl-2 over-expression extends culture longevity from 6 days to at least 15 days by suppressing the specific rate of early apoptotic cell formation by more than 6-fold and necrotic cell formation by at least 3-fold, despite nearly a 3-fold decrease in initial cell growth rate and no significant change in the specific rate of late apoptotic cell formation. This computational analysis supports a mechanism in which Bcl-2 is a common mediator of early apoptotic and necrotic events occurring at rates that are dependent on cellular factors accumulating over time. The model has current application to the rational design of cell cultures through metabolic engineering for the industrial production of biopharmaceuticals.
Authors:
Kim C O'Connor; James W Muhitch; Daniel J Lacks; Mohamed Al-Rubeai
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-09-19
Journal Detail:
Title:  Biotechnology letters     Volume:  28     ISSN:  1573-6776     ISO Abbreviation:  Biotechnol. Lett.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-09-18     Revised Date:  2008-10-07    
Medline Journal Info:
Nlm Unique ID:  8008051     Medline TA:  Biotechnol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1919-24     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 70118, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Cell Death
Cell Line, Tumor
Cell Survival
Computational Biology / methods
Gene Expression Regulation, Neoplastic*
Humans
Kinetics
Models, Statistical
Multiple Myeloma / metabolism*,  pathology
Necrosis
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Software
Thymidine / chemistry
Time Factors
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 50-89-5/Thymidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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