title: Chemostat-based transcriptional analysis of growth rate change and BCL-2 over-expression in NS0 cells.
abstract: We investigated the transcriptional response of NS0 cells undergoing controlled nutrient growth change in continuous chemostat culture using mouse microarrays. A 50% reduction in growth rate resulted in detectable alterations in the expression of 29 genes in NS0 cells. Notably, expression of genes in three major biological processes, namely transcriptional, translational, and protein processing functions, were modified. To further elucidate the advantage of the chemostat environment for establishment of "omic" data sets, an expression profile of the over-expressed gene bcl-2 in NS0 cells was probed. Functional analysis revealed that the underlying altered molecular mechanism was particularly associated with G1 cell cycle progression, protein synthesis, and apoptosis. Importantly, these findings agreed with the physical function of the cells. Despite an increase in survival rate, bcl-2 over-expression resulted in a decrease of specific productivity, glucose consumption, oxygen uptake rate and intracellular protein content, indicating a lower energy generating metabolism. Further, a prolongation of G1 cell cycle phase was evident on lowering the growth rate. Overall, the application of microarray analysis to chemostat-grown cultures offers an excellent combination for the interpretation of transcriptomic profiles to elucidate the molecular mechanisms during nutrient growth change and bcl-2 over-expression.
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Republic of Ireland.
authors.forename: Britta
authors.initials: B
authors.lastname: Krampe
authors.forename: Ailís
authors.initials: A
authors.lastname: Fagan
authors.forename: Peadar Ó
authors.initials: PÓ
authors.lastname: Gaora
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Rubeai
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D020869:Gene Expression Profiling / Q000379:methods*; D005947:Glucose / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; C052617:Bcl2 protein, mouse; D005947:Glucose; D010100:Oxygen