Short-Chain Fatty Acids Activate AMP-Activated Protein Kinase and Ameliorate Ethanol-Induced Intestinal Barrier Dysfunction in Caco-2 Cell Monolayers
| العنوان: | Short-Chain Fatty Acids Activate AMP-Activated Protein Kinase and Ameliorate Ethanol-Induced Intestinal Barrier Dysfunction in Caco-2 Cell Monolayers |
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| المؤلفون: | Ad A.M. Masclee, Harm-Jan Pieters, Elhaseen Elamin, Jan Dekker, Daisy Jonkers |
| المساهمون: | RS: NUTRIM - R2 - Gut-liver homeostasis, Interne Geneeskunde |
| المصدر: | Journal of Nutrition, 143(12), 1872-1881. Oxford University Press The Journal of Nutrition 143 (2013) 12 The Journal of Nutrition, 143(12), 1872-1881 |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | signaling pathway, Small interfering RNA, colonic function, epithelial-cells, DIETARY FIBER, leaky gut, Medicine (miscellaneous), Butyrate, AMP-Activated Protein Kinases, Occludin, chemistry.chemical_compound, BUTYRATE, AMP-activated protein kinase, Dichlorofluorescein, ALCOHOLIC LIVER-DISEASE, Humans, oxidative stress, Intestinal Mucosa, OXIDATIVE STRESS, COLONIC FUNCTION, Barrier function, chemistry.chemical_classification, Nutrition and Dietetics, Ethanol, biology, Fatty Acids, AMPK, induced gut leakiness, LEAKY GUT, EPITHELIAL-CELLS, PARACELLULAR PERMEABILITY, butyrate, dietary fiber, Molecular biology, Enzyme Activation, paracellular permeability, chemistry, Biochemistry, INDUCED GUT LEAKINESS, Propionate, biology.protein, Departement Dierwetenschappen, alcoholic liver-disease, SIGNALING PATHWAY, Caco-2 Cells, Department of Animal Sciences |
| الوصف: | Short-chain fatty acids (SCFAs) have been shown to promote intestinal barrier function, but their protective effects against ethanol-induced intestinal injury and underlying mechanisms remain essentially unknown. The aim of the study was to analyze the influence of SCFAs on ethanol-induced barrier dysfunction and to examine the role of AMP-activated protein kinase (AMPK) as a possible mechanism using Caco-2 monolayers. The monolayers were treated apically with butyrate (2, 10, or 20 mmol/L), propionate (4, 20, or 40 mmol/L), or acetate (8, 40, or 80 mmol/L) for 1 h before ethanol (40 mmol/L) for 3 h. Barrier function was analyzed by measurement of transepithelial resistance and permeation of fluorescein isothiocyanate-labeled dextran. Distribution of the tight junction (TJ) proteins zona occludens-1, occludin, and filamentous-actin (F-actin) was examined by immunofluorescence. Metabolic stress was determined by measuring oxidative stress, mitochondrial function, and ATP using dichlorofluorescein diacetate, dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, and bioluminescence assay, respectively. AMPK was knocked down by small interfering RNA (siRNA), and its activity was assessed by a cell-based ELISA. Exposure to ethanol significantly impaired the barrier function compared with controls (P < 0.0001) and disrupted the TJ and F-actin cytoskeleton integrity and induction of metabolic stress. However, pretreatment with 2 mmol/L butyrate, 4 mmol/L propionate, and 8 mmol/L acetate significantly alleviated the ethanol-induced barrier dysfunction, TJ and F-actin disruption, as well as metabolic stress compared with ethanol-exposed monolayers (P < 0.0001). The promoting effects on barrier function were abolished by inhibiting AMPK using either compound C or siRNA. These observations indicate that SCFAs exhibit protective effects against ethanol-induced barrier disruption via AMPK activation, suggesting a potential for SCFAs as prophylactic and/or therapeutic factors against ethanol-induced gut leakiness. |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 0022-3166 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6fcdaf31b6a8fad173f9fdb87baeea2d https://cris.maastrichtuniversity.nl/en/publications/15a8996e-9a0f-4088-b6e8-ccf6e599b4c2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6fcdaf31b6a8fad173f9fdb87baeea2d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00223166 |
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