Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line
Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line
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DOI：
10.1007/s10142-006-0043-2
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发表时间：
2007-07-01
影响因子：
2.9
通讯作者：
Elsasser, Ted H.
中科院分区：
文献类型：
--
作者：
Li, Cong-jun;Li, Robert W.;Elsasser, Ted H.
反刍动物已经进化到代谢短链挥发性脂肪酸（VIA），乙酸，丙酸和丁酸，以满足高达70%的营养能量需求。利用反刍动物细胞固有的VIA依赖性来增加丁酸盐基因反应元件在调节生化途径中的作用的研究的敏感性水平。利用高密度寡核苷酸芯片技术研究了丁酸钠对牛肾上皮细胞基因表达的调控。丁酸诱导细胞生长停滞和凋亡的详细机制进行了分析，使用的不可逆性途径知识库。对基因芯片数据的功能分类和通路分析显示，4条经典通路（细胞周期：G2/M期DNA损伤检查点和嘧啶代谢; G1/S期检查点调控和嘌呤代谢）受到显著干扰。这些基因的生物学相关网络和途径也被确定。- IGF 2、TGFB 1、TP 53、E2 F4和CDC 2被确定为集中在这些基因组网络中。目前的研究结果提供了一个基础，了解丁酸盐在动物细胞生长，增殖和能量代谢中可能发挥的生物学作用和分子机制。
Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VIA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient energy requirements. The inherent VIA 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.