Overexpression of @entity1 intestinal oligopeptide transporter in XXXX cells via adenoviral transduction.

@entity1 @entity1522 @entity3405 @entity37537 @entity36900 @entity281 @entity7265 @entity35 @entity9881
PURPOSE: Our goals are to establish an in vitro screening system and to evaluate a new approach in improving oral absorption of peptides and peptide-like drugs by overexpression of the @entity1 intestinal oligopeptide transporter ( @entity37537 ). This study characterizes the expression of @entity37537 in @entity1 intestinal Caco-2 cells, @entity35 intestinal epithelial cells (IEC-18), and @entity1 cervix epithelial cells (Hela) after adenoviral transduction. METHODS: A recombinant replication-deficient adenovirus carrying the @entity37537 gene was made and used as a vector for the expression of @entity37537 . The increase in the uptake permeability of @entity7265 and @entity36900 was determined. The effects of time, dose, apical pH, and substrate specificity were evaluated. RESULTS: A significant increase in the uptake permeability of @entity36900 and @entity7265 was found in all three cell lines after viral transduction. The increase of @entity36900 permeability in Hela. IEC-18, and Caco-2 cells was 85-, 46-, and 15-fold respectively. Immunoblotting using an antibody against @entity37537 detected high levels of a 85-98-kDa protein in all three infected cell lines. Substrate permeability was dependent on time of @entity281 , inward pH gradients, and multiplicity of @entity281 (MOI). @entity281 and lower @entity37537 expression were observed in differentiated Caco-2 cells. The uptake was inhibited by @entity9881 and @entity3405 antibiotics but not @entity1522 . CONCLUSIONS: @entity281 Hela cells displayed a pronounced level of @entity37537 expression with a low background and high specificity to @entity9881 . These features make this system a useful tool for screening of potential substrates. The success of overexpression of @entity37537 in Caco-2 and IEC-18 cells may lead to a novel approach in improving oral absorption of peptides and peptidornimetic drugs.
