The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation
The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation
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DOI：
10.1074/jbc.m302932200
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发表时间：
2003-08-01
影响因子：
4.8
通讯作者：
Cascante, M
中科院分区：
文献类型：
--
作者：
Boren, J;Lee, WNP;Cascante, M
本文采用基于稳定同位素的动态代谢谱分析方法，探讨丁酸盐诱导HT29细胞分化的机制。我们利用[1,2- c -13(2)]葡萄糖或[1,2- c -13(2)]丁酸盐作为单一示踪剂培养丁酸盐敏感（HT29）细胞，观察这些细胞代谢通量的变化。在HT29细胞中，丁酸盐浓度的增加以剂量依赖的方式抑制葡萄糖摄取、葡萄糖氧化和核酸核糖合成。葡萄糖碳利用的脂肪酸合成和三羧酸循环通量被丁酸盐取代。我们还证明这些变化不存在于丁酸盐抗性胰腺腺癌MIA细胞中。结果表明，结肠癌细胞获得分化表型的机制是通过葡萄糖取代丁酸盐作为大分子生物合成和能量生产的主要碳源。这为HT29细胞在丁酸盐作用下通过代谢适应性变化进行细胞分化提供了更好的理解，表明代谢途径底物流动的变化是肿瘤细胞增殖和分化的有力调节剂。
Stable isotope-based dynamic metabolic profiling is applied in this paper to elucidate the mechanism by which butyrate induces cell differentiation in HT29 cells. We utilized butyrate-sensitive ( HT29) cells incubated with [1,2-C-13(2)] glucose or [1,2-C-13(2)] butyrate as single tracers to observe the changes in metabolic fluxes in these cells. In HT29 cells, increasing concentrations of butyrate inhibited glucose uptake, glucose oxidation, and nucleic acid ribose synthesis in a dose-dependent fashion. Glucose carbon utilization for de novo fatty acid synthesis and tricarboxylic acid cycle flux was replaced by butyrate. We also demonstrated that these changes are not present in butyrate-resistant pancreatic adenocarcinoma MIA cells. The results suggest that the mechanism by which colon carcinoma cells acquire a differentiated phenotype is through a replacement of glucose for butyrate as the main carbon source for macromolecule biosynthesis and energy production. This provides a better understanding of cell differentiation through metabolic adaptive changes in response to butyrate in HT29 cells, demonstrating that variations in metabolic pathway substrate flow are powerful regulators of tumor cell proliferation and differentiation.