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.

[1]  M. Bugaut.  Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals. , 1987, Comparative biochemistry and physiology. B, Comparative biochemistry.

[2]  E. N. Bergman.  Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. , 1990, Physiological reviews.

[3]  C. Paraskeva,et al.  The short-chain fatty acid butyrate induces apoptosis in colorectal tumour cell lines. , 1995, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[4]  W. Scheppach,et al.  Role of short-chain fatty acids in the prevention of colorectal cancer. , 1995, European journal of cancer.

[5]  G. Evan,et al.  A License to Kill , 1996, Cell.

[6]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  B. Dubray,et al.  Histopathological and cellular studies of a case of cutaneous radiation syndrome after accidental chronic exposure to a cesium source. , 1999, Radiation research.

[8]  M. Sussman,et al.  Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array , 1999, Nature Biotechnology.

[9]  G. Calaf,et al.  Short-chain fatty acids inhibit invasive human colon cancer by modulating uPA, TIMP-1, TIMP-2, mutant p53, Bcl-2, Bax, p21 and PCNA protein expression in an in vitro cell culture model. , 2001, The Journal of nutrition.

[10]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  E. Cabré,et al.  Nutrition in inflammatory bowel disease , 2001, Current opinion in clinical nutrition and metabolic care.

[12]  M. DePamphilis,et al.  Mammalian Orc1 Protein Is Selectively Released from Chromatin and Ubiquitinated during the S-to-M Transition in the Cell Division Cycle , 2002, Molecular and Cellular Biology.

[13]  I. Johnson,et al.  Anticarcinogenic effects of diet-related apoptosis in the colorectal mucosa. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[14]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[15]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[16]  L. Augenlicht,et al.  Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. , 2003, Molecular cancer research : MCR.

[17]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[18]  Jerry M. Adams,et al.  Ways of dying: multiple pathways to apoptosis. , 2003, Genes & development.

[19]  M. Yin,et al.  TGF-β1 Regulates Lymphocyte Homeostasis by Preventing Activation and Subsequent Apoptosis of Peripheral Lymphocytes1 , 2003, The Journal of Immunology.

[20]  D. Faller,et al.  Short-chain fatty acid inhibitors of histone deacetylases: promising anticancer therapeutics? , 2003, Current cancer drug targets.

[21]  A. Williams,et al.  IGFBP-3 and apoptosis—a licence to kill? , 2001, Apoptosis.

[22]  S. Korsmeyer,et al.  Review Cell Death: Critical Control Points Another Line of Evidence for the Importance of Caspases in Cell Death Came From , 2022 .

[23]  M. DePamphilis,et al.  Role for Cdk1 (Cdc2)/Cyclin A in Preventing the Mammalian Origin Recognition Complex's Largest Subunit (Orc1) from Binding to Chromatin during Mitosis , 2004, Molecular and Cellular Biology.

[24]  千葉 哲博.  Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells , 2004 .

[25]  John D. Storey,et al.  A network-based analysis of systemic inflammation in humans , 2005, Nature.

[26]  T. Elsasser,et al.  Butyrate-induced apoptosis and cell cycle arrest in bovine kidney epithelial cells: involvement of caspase and proteasome pathways. , 2005, Journal of animal science.

[27]  Sung-Dae Cho,et al.  Ras/MAP kinase pathways are involved in Ras specific apoptosis induced by sodium butyrate. , 2005, Cancer letters.

[28]  K. Somasundaram,et al.  Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate , 2005, International journal of cancer.

[29]  Claes Wahlestedt,et al.  Considerations when using the significance analysis of microarrays (SAM) algorithm , 2005, BMC Bioinformatics.

[30]  A. Watson.  An overview of apoptosis and the prevention of colorectal cancer. , 2006, Critical reviews in oncology/hematology.

[31]  Robert W. Li,et al.  Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells , 2006, BMC Genomics.

[32]  E. Ho,et al.  Dietary agents as histone deacetylase inhibitors , 2006, Molecular carcinogenesis.

[33]  Robert W. Li,et al.  Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis. , 2006, Physiological genomics.

[34]  Qi-Fu Li,et al.  Effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. , 2006, World journal of gastroenterology.

[35]  Y. Tabuchi,et al.  Genetic networks responsive to sodium butyrate in colonic epithelial cells , 2006, FEBS letters.

[36]  E. Ho,et al.  Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? , 2006, Carcinogenesis.

[37]  Lakshmanan K. Iyer,et al.  A combined approach to data mining of textual and structured data to identify cancer-related targets , 2006, BMC Bioinformatics.

[38]  D. Spandidos,et al.  Expression analysis of peptide growth factors VEGF, FGF2, TGFB1, EGF and IGF1 in prostate cancer and benign prostatic hyperplasia. , 2006, International journal of oncology.

[39]  K. Tsuneyama,et al.  High-density oligonucleotide microarrays and functional network analysis reveal extended lung carcinogenesis pathway maps and multiple interacting genes in NNK [4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone] induced CD1 mouse lung tumor , 2006, Journal of Cancer Research and Clinical Oncology.

[40]  R. Dashwood,et al.  Histone deacetylases as targets for dietary cancer preventive agents: lessons learned with butyrate, diallyl disulfide, and sulforaphane. , 2006, Current drug targets.

[41]  Anatoly L. Mayburd,et al.  Ingenuity Network-Assisted Transcription Profiling: Identification of a New Pharmacologic Mechanism for MK886 , 2006, Clinical Cancer Research.

[42]  C. Paraskeva,et al.  Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-κB , 2007, Cell Death and Differentiation.

[43]  R. Lloyd,et al.  Regulation of cell growth and expression of 7B2, PC2, and PC1/3 by TGFβ 1 and sodium butyrate in a human pituitary cell line (HP75) , 2003, Endocrine.

[44]  J. Affourtit,et al.  Selective degradation of transcripts during meiotic maturation of mouse oocytes. , 2007, Developmental biology.

[45]  C. Paraskeva,et al.  Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. , 2007, Cell death and differentiation.