Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function

The Journal of Biological Chemistry
J Scott LeeSean P Colgan

Abstract

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 i...Continue Reading

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Citations

May 10, 2019·International Journal of Molecular Sciences·Kamal M YakoubValentina Di Pietro
Jul 30, 2020·Molecular Biology of the Cell·Alexander S DowdellSean P Colgan
Oct 7, 2019·Inflammatory Bowel Diseases·Olga Maria NardoneMarietta Iacucci
May 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ruth X WangSean P Colgan

Related Concepts

Metazoa
Colitis
Taenia Coli
Energy Metabolism
Structure of Intestinal Gland
Mice, Inbred C57BL
Oxygen Consumption
Permeability
Tight Junctions
Hypoxanthine

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