Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in XXXX .

@entity1944 @entity1797 @entity19 @entity185 @entity1960 @entity8582 @entity460 @entity14
UNASSIGNED: Chitosan oligosaccharide (COS), a biomaterial derived from chitin, is absorbed by intestinal epithelia without @entity1797 and has diverse biological activities including intestinal epithelial function. However, the mode of action is still unclear. This study aimed to investigate the effect of COS on @entity8582 -activated protein kinase (AMPK) in intestinal epithelial cells (IEC) and its potential applications in the @entity1944 benefited from AMPK activation. COS with molecular weights (MW) from 5,000Da to 14,000Da induced AMPK activation in T84 cells. That with MW of 5,000-Da was the most potent polymer and was used in the subsequent experiments. COS also activated AMPK in other IEC including HT-29 and Caco-2 cells. Mechanism of COS-induced AMPK activation in T84 cells involves @entity460 -sensing receptor (CaSR)-phospholipase C (PLC)-IP3 receptor channel-mediated @entity460 release from endoplasmic reticulum (ER). In addition, COS promoted tight junction assembly in T84 cells in an AMPK-dependent manner. COS also inhibited NF-kB transcriptional activity and NF-kB-mediated inflammatory response and barrier disruption via AMPK-independent mechanisms. Interestingly, luminal exposure to COS suppressed cholera toxin-induced intestinal fluid secretion by    30% concurrent with AMPK activation in a @entity19 closed loop model. Importantly, oral administration of COS prevented the development of aberrant crypt foci in a @entity19 model of @entity1960 -associated @entity14 ( @entity14 ) via a mechanism involving AMPK activation-induced b-catenin suppression and @entity185 activation. Collectively, this study reveals a novel action of COS in activating AMPK via CaSR-PLC-IP3 receptor channel-mediated @entity460 release from ER. COS may be beneficial in the treatment of secretory diarrheas and @entity14 chemoprevention.
