FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER

纤维、短链脂肪酸与结肠癌

• 批准号: 2712680
• 负责人: JOANNE R LUPTON
• 金额: $ 6.7万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2712680
• 关键词: acidity /alkalinity; adenosine triphosphate; autoradiography; cancer prevention; carcinogenesis inhibitor; chemical carcinogen; chemoprevention; colon neoplasms; complementary DNA; confocal scanning microscopy; dietary fiber; gas chromatography; high performance liquid chromatography; laboratory rat; membrane lipids; neoplasm /cancer nutrition therapy; nonhuman therapy evaluation; northern blottings; nutrition aspect of cancer; nutrition related tag; protein isoforms; short chain fatty acid; western blottings

The broad scientific goal of this interactive research program is to evolve a systematic biochemical understanding of how the consumption of fibers, fats, and proteins results in colonic epithelial cells that are more or less susceptible to chemical carcinogens. The focus of this proposal is on short chain fatty acids (SCFA) which are the products of fiber fermentation. Using cells from both carcinogen-treated and saline control animals, we propose to characterize how uptake of SCFA into colonocytes changes the biochemistry of these cells in such a way that their proliferative status is altered. The three important changes in biological/biochemical states that will be investigated are: (1) changes in intracellular pH; (2) changes in colonocyte metabolism (including energy status); and (3) changes in membrane lipids that result in changes in signal transduction pathways (specifically Protein Kinase C, isoforms and subcellular localization). Since there is good evidence that the effect of SCFA on colonocytes is different in normal cells vs transformed cells, experiments will be conducted in both cell types. Further, since the proximal and distal colon have different cell kinetics and SCFA absorption patterns, they will be treated as separate tissues. The data generated will elucidate how intracellular pH, colonocyte metabolism, and intracellular signaling mechanisms, which regulate epithelial cytokinetics, are influenced by different types and amounts of SCFA characterization of each part of this complex process should provide important information on the basic biology of colonocytes. Elucidation of the fundamental mechanisms regulating colonic epithelial cytokinetics is essential if diet is to be established as a legitimate colon cancer prevention strategy.

该互动研究计划的广泛科学目标是 进化系统地了解如何消费 纤维，脂肪和蛋白质会导致结肠上皮细胞 或多或少容易受到化学致癌物的影响。重点 建议是在短链脂肪酸（SCFA）上 纤维发酵。使用来自致癌物和盐水的细胞 控制动物，我们建议表征SCFA的吸收 结肠细胞改变这些细胞的生物化学，以至于 它们的增殖状态发生了变化。三个重要的变化 将要研究的生物/生化状态是： （1）细胞内pH的变化； （2）结肠细胞代谢的变化（包括能量状态）；和 （3）导致信号变化的膜脂质的变化 转导途径（特别是蛋白激酶C，同工型和 亚细胞定位）。 由于有充分的证据表明SCFA对结肠细胞的影响是 正常细胞与转化的细胞不同，实验将是 在两种细胞类型中进行。此外，由于近端和远端结肠 具有不同的细胞动力学和SCFA吸收模式，它们将是 被视为单独的组织。生成的数据将阐明如何 细胞内pH，结肠细胞代谢和细胞内信号传导 调节上皮细胞动力学的机制受到 每个部分的不同类型和数量的SCFA表征 复杂的过程应提供有关基本生物学的重要信息 结肠细胞。 阐明调节的基本机制 如果要确定饮食，则必须进行结肠上皮细胞动力学 作为合法的结肠癌预防策略。