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Chitooligosaccharide inhibits cyst formation and enlargement through calcium restoration and AMPK activation
Author(s) -
Tuangpholkrung Phattharaphon,
Muanprasat Chatchai,
Chatsudthipong Varanuj
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1032.6
Subject(s) - ampk , intracellular , calcium in biology , chemistry , cyst , endocrinology , medicine , calcium , protein kinase a , biology , kinase , biochemistry , pathology
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disease. It is developed from mutation in renal Pkd1 or/and Pkd2 gene leading to decreased intracellular calcium and consequently cysts formation. These renal cysts replace normal parenchyma cells disrupting its function that could lead to end‐stage renal failure. Currently, no effective therapy is available for PKD treatment. Recently, activation of AMP‐activated protein kinase (AMPK) by Metformin was found to inhibit cell proliferation and also reduce fluid secretion via CFTR in Madin‐Darby Canine Kidney (MDCK) cell. Interestingly, our group has shown that chitooligosaccharide or COS, the derivative of chitosan, could activate AMPK via the mechanism involved an elevation of intracellular calcium in colon cancer cell. Therefore, we hypothesized that COS‐activated AMPK may inhibit cyst formation and growth in MDCK cyst model. The results of toxicity test indicated that COS at the concentrations of 50, 100, 200 and 500 μg/ml produced no toxic effect to cells. In contrast, it was found that the treatments with COS at concentrations of 100, 200 and 500 μg/ml markedly decreased both cyst formation and cyst growth. Minimum effective dose of COS (100 μg/ml) was selected to study for its underlying mechanisms. Western blot analysis showed that COS at concentration of 100 μg/ml could activate AMPK and its downstream protein, acetyl Co‐A carboxylase (ACC). COS also induced an elevation in intracellular calcium. These data indicated that COS was able to inhibit cyst formation and retard cyst enlargement, in part, by the restoration of intracellular calcium and activation of AMPK. Support or Funding Information This work was supported by Development and Promotion of Science and Technology Talents Project (DPST), Institute for the Promotion of Teaching Science and Technology (to PT), and Faculty of Science, Mahidol University, Thailand.