کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3841700 | 1247996 | 2007 | 12 صفحه PDF | دانلود رایگان |

To investigate how intestinal epithelial cells respond to contact with Candida albicans, an organism able to invade the bloodstream via the gastrointestinal tract, we focused on the junction proteins occludin, E-cadherin, and desmoglein-2. The levels of these 3 junction proteins were reduced in lysates of human intestinal epithelial monolayers (Caco-2) after a 24-h inoculation with C. albicans, compared with lysates from Saccharomyces cerevisiae-inoculated monolayers. Treatment with pepstatin A did not change the effect of C. albicans on full-length occludin, desmoglein-2, and E-cadherin; however, pepstatin A enhanced the accumulation of a 35-kDa fragment derived from the intracellular portion of E-cadherin. This 35-kDa fragment also accumulated in the presence of γ-secretase inhibitors. These observations suggest that enhancement of E-cadherin cleavage by C. albicans generates an intracellular E-cadherin fragment that can serve as a substrate for γ-secretase. An 89-kDa extracellular fragment of E-cadherin was detected in supernatants of C. albicans-inoculated monolayers; this cleavage event was insensitive to both pepstatin A and γ-secretase inhibitors. Transepithelial electrical resistance, a measure of monolayer integrity, decreased significantly and synchronously with increased generation of the 89-kDa extracellular E-cadherin fragment. Cleavage of E-cadherin may destabilize the homotypic interactions between adjacent epithelial cells and could contribute to loss of monolayer integrity. These experiments identify 2 E-cadherin cleavage events that are enhanced by contact with C. albicans: an intracellular cleavage event that generates a substrate for γ-secretase and an extracellular cleavage event that is temporally associated with an increase in monolayer permeability.
Journal: Translational Research - Volume 149, Issue 4, April 2007, Pages 211–222