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Giardia‐induced intestinal epithelial apoptosis is rescued by SGLT‐1‐mediated glucose uptake
Author(s) -
Yu Linda ChiaHui,
Turner Jerrold R.,
Buret Andre G
Publication year - 2007
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.21.5.a586-a
Subject(s) - enterocyte , apoptosis , giardia , cotransporter , biology , dna fragmentation , cytoprotection , glucose uptake , programmed cell death , microbiology and biotechnology , chemistry , biochemistry , endocrinology , small intestine , sodium , insulin , organic chemistry
Giardiasis is a common waterborne diarrheal disease. Previous study has shown that exposure to giardia products induces apoptosis and barrier defects in enterocytes. The sodium‐dependent glucose cotransporter (SGLT)‐1‐ mediated glucose uptake protects enterocytes against cell death induced by bacterial LPS. The aim of this project is to examine whether enhanced SGLT‐1 activity may also rescue enterocytes from giardia‐induced apoptosis. SGLT‐1‐transfected Caco‐2 cells were exposed to giardia products in low (5 mM) or high (25 mM) glucose media. Exposure to giardia products induced caspase‐3 enzymatic activity and DNA fragmentation in these cells in low glucose environments. These apoptotic phenomena were abolished in the presence of high glucose. Giardia products increased SGLT‐1 activity in dose‐ and time‐dependent manner, associated with increase of Vmax and enhanced apical expression of SGLT‐1 on cells. This giardia‐induced increased glucose uptake was inhibited by colchicine, suggesting a microtubule‐dependent translocation of SGLT‐1 onto the apical surface. Addition of phloridzin, which competitively binds to SGLT‐1, inhibited the cytoprotection mediated by high glucose. Overall, enhanced SGLT‐1‐mediated glucose uptake protected epithelial cell against giardia‐induced apoptosis. This cytoprotective mechanism may be responsible for maintaining epithelial homeostasis upon a range of pathogenic challenges.