采用基于 1H-NMR 的代谢组学方法研究用西地孕酮处理的 Caco-2 细胞在肠道疾病中的代谢变化。

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-10-16 DOI:10.1002/biof.2132
Mo-Rong Xu, Chia-Hsin Lin, Chung Hsuan Wang, Sheng-Yang Wang
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引用次数: 0

摘要

线粒体功能障碍可能导致肠道功能紊乱,而炎症性肠病则表现为影响胃肠道的慢性炎症。这种疾病会破坏肠上皮细胞的屏障功能,并改变代谢产物。增加肠上皮细胞线粒体三磷酸腺苷(ATP)的合成是治疗结肠炎的一个很有前景的途径。然而,西地孕酮对 ATP 和肠道屏障的影响仍有待探索。因此,本研究致力于探讨西地孕酮对炎症鸡尾酒(IC)诱导的 Caco-2 细胞肠上皮屏障功能障碍的保护作用。研究结果表明,西地孕酮能提高肠上皮屏障的 ATP 含量和跨上皮电阻值。此外,西地孕酮还能缓解 IC 诱导的紧密连接蛋白(ZO-1、Occludin 和 Claudin-1)信使核糖核酸(mRNA)表达的减少,从而改善肠上皮屏障功能障碍。此外,基于核磁共振(NMR)的代谢组学分析表明,暴露于 IC 的 Caco-2 细胞可通过西地孕酮治疗得到恢复。值得注意的是,西地孕酮能提高氨基酸等代谢物的含量,从而增强肠道屏障。总之,西地孕酮通过促进 Caco-2 细胞的 ATP 依赖性增殖和提高氨基酸水平以维持紧密连接信使核糖核酸的表达,缓解了 IC 引起的肠上皮屏障功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigate the metabolic changes in intestinal diseases by employing a 1H-NMR-based metabolomics approach on Caco-2 cells treated with cedrol.

Mitochondrial dysfunction may precipitate intestinal dysfunction, while inflammatory bowel disease manifests as a chronic inflammatory ailment affecting the gastrointestinal tract. This condition disrupts the barrier function of the intestinal epithelium and alters metabolic products. Increasing mitochondrial adenosine triphosphate (ATP) synthesis in intestinal epithelial cells presents a promising avenue for colitis treatments. Nevertheless, the impact of cedrol on ATP and the intestinal barrier remains unexplored. Hence, this study is dedicated to examining the cedrol's protective effect on an inflammatory cocktail (IC)-induced intestinal epithelial barrier dysfunction in Caco-2 cells. The finding reveals that cedrol enhances ATP content and the transepithelial electrical resistance value in the intestinal epithelial barrier. Moreover, cedrol mitigates the IC-induced decrease in the messenger ribonucleic acid (mRNA) expression of tight junction proteins (ZO-1, Occludin, and Claudin-1), thereby ameliorating intestinal epithelial barrier dysfunction. Furthermore, nuclear magnetic resonance (NMR)-based metabolomic analysis indicated that IC-exposed Caco-2 cells are restored by cedrol treatments. Notably, cedrol elevates metabolites such as amino acids, thereby enhancing the intestinal barrier. In conclusion, cedrol alleviates IC-induced intestinal epithelial barrier dysfunction by promoting ATP-dependent proliferation of Caco-2 cells and bolstering amino acid levels to sustain tight junction messenger ribonucleic acid expression.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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