دورية أكاديمية
Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function.
| العنوان: | Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function. |
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| المؤلفون: | Lee JS; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and., Wang RX; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and., Alexeev EE; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and., Lanis JM; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and., Battista KD; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and., Glover LE; the School of Medicine, University College Dublin, Dublin, Ireland., Colgan SP; From the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and sean.colgan@ucdenver.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2018 Apr 20; Vol. 293 (16), pp. 6039-6051. Date of Electronic Publication: 2018 Feb 27. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Energy Metabolism*, Colitis/*metabolism , Colon/*metabolism , Hypoxanthine/*metabolism , Intestinal Mucosa/*metabolism, Animals ; Colitis/pathology ; Colon/pathology ; Female ; Intestinal Mucosa/pathology ; Metabolome ; Mice ; Mice, Inbred C57BL ; Oxygen Consumption ; Permeability ; Tight Junctions/metabolism ; Tight Junctions/pathology |
| مستخلص: | Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking. Here, to delineate barrier-related energy flux, we developed an HPLC-based profiling method to track changes in energy flux and adenylate metabolites during barrier development and restoration. Cultured epithelia exhibited pooling of phosphocreatine and maintained ATP during barrier development. EDTA-induced epithelial barrier disruption revealed that hypoxanthine levels correlated with barrier resistance. Further studies uncovered that hypoxanthine supplementation improves barrier function and wound healing and that hypoxanthine appears to do so by increasing intracellular ATP, which improved cytoskeletal G- to F-actin polymerization. Hypoxanthine supplementation increased the adenylate energy charge in the murine colon, indicating potential to regulate adenylate energy charge-mediated metabolism in intestinal epithelial cells. Moreover, experiments in a murine colitis model disclosed that hypoxanthine loss during active inflammation correlates with markers of disease severity. In summary, our results indicate that hypoxanthine modulates energy metabolism in intestinal epithelial cells and is critical for intestinal barrier function. (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.) |
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| معلومات مُعتمدة: | P30 DK048520 United States DK NIDDK NIH HHS; F32 DK122741 United States DK NIDDK NIH HHS; T32 GM136444 United States GM NIGMS NIH HHS; R01 DK050189 United States DK NIDDK NIH HHS; F30 DK120072 United States DK NIDDK NIH HHS; R01 DK104713 United States DK NIDDK NIH HHS; R01 DK103712 United States DK NIDDK NIH HHS; I01 BX002182 United States BX BLRD VA; R29 DK050189 United States DK NIDDK NIH HHS; R37 DK050189 United States DK NIDDK NIH HHS; R01 DK095491 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: barrier function; colitis; cytoskeleton; energy metabolism; epithelia; intestinal epithelium; intestinal metabolism; tight junction |
| المشرفين على المادة: | 2TN51YD919 (Hypoxanthine) |
| تواريخ الأحداث: | Date Created: 20180301 Date Completed: 20190108 Latest Revision: 20231103 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5912467 |
| DOI: | 10.1074/jbc.RA117.000269 |
| PMID: | 29487135 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
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| DOI: | 10.1074/jbc.RA117.000269 |