title: SGLT-1-mediated glucose uptake protects human intestinal epithelial cells against Giardia duodenalis-induced apoptosis.
abstract: Infection with Giardia duodenalis is one of the most common causes of waterborne diarrheal disease worldwide. Mechanisms of pathogenesis and host response in giardiasis remain incompletely understood. Previous studies have shown that exposure to G. duodenalis products induce apoptosis in enterocytes. We recently discovered that sodium-dependent glucose cotransporter (SGLT)-1-mediated glucose uptake modulates enterocytic cell death induced by bacterial lipopolysaccharide. The aim of this study was to examine whether enhanced epithelial SGLT-1 activity may constitute a novel mechanism of host defense against G. duodenalis-induced apoptosis. SGLT-1-transfected Caco-2 cells were exposed to G. duodenalis products in low (5mM) or high (25mM) glucose media. In low glucose environments, G. duodenalis-induced caspase-3 activation and DNA fragmentation in these cells. These apoptotic phenomena were abolished in the presence of high glucose. A soluble proteolytic fraction of G. duodenalis was found to upregulate SGLT-1-mediated glucose uptake in a dose- and time-dependent manner, in association with increased apical SGLT-1 expression on epithelial cells. Kinetic analysis showed that this phenomenon resulted from an increase in the maximal rate of sugar transport (V(max)) by SGLT-1, with no change in the affinity constant (K(m)). The addition of phloridzin (a competitive inhibitor for glucose binding to SGLT-1) abolished the anti-apoptotic effects exerted by high glucose. Together, the findings indicate that SGLT-1-dependent glucose uptake may represent a novel epithelial cell rescue mechanism against G. duodenalis-induced apoptosis.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB, Canada T2N 1N4.
authors.forename: Linda C H
authors.initials: LC
authors.lastname: Yu
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Huang
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Kuo
authors.forename: Heather
authors.initials: H
authors.lastname: Sayer
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.forename: Andre G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001692:Biological Transport; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000378:metabolism*; D016829:Giardia lamblia / Q000502:physiology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000469:parasitology; D007421:Intestine, Small / Q000378:metabolism* / Q000469:parasitology; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051269:Sodium-Glucose Transporter 1; D005947:Glucose