Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line.
Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VFA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient energy requirements. The inherent VFA dependence of ruminant cells was exploited to add a level of increased sensitivity to the study of the role of butyrate gene-response elements in regulatory biochemical pathways. Global gene expression profiles of the bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The detailed mechanisms by which butyrate induces cell growth arrest and apoptosis were analyzed using the Ingenuity Pathways Knowledge Base. The functional category and pathway analyses of the microarray data revealed that four canonical pathways (Cell cycles: G2/M DNA damage checkpoint, and pyrimidine metabolism; G1/S checkpoint regulation and purine metabolism) were significantly perturbed. The biologically relevant networks and pathways of these genes were also identified. IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these genomic networks. The present findings provide a basis for understanding the full range of the biological roles and the molecular mechanisms that butyrate may play in animal cell growth, proliferation, and energy metabolisms.
Li
Cong-jun
CJ
Growth Biology Laboratory, Animal and Natural Resources Institute/ARS, U.S. Derpartment of Agriculture, 10300 Baltimore Avenue, BARC East, Beltsville, MD 20705, USA. cli@anri.barc.usda.gov
Li
Robert W
RW
Wang
Yong-hong
YH
Elsasser
Ted H
TH
D000818:Animals; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects*; D007668:Kidney / Q000166:cytology
D002087:Butyrates; D005232:Fatty Acids, Volatile