M1703 Intestinal Permeability and Bacterial Translocation Are Modulated By the Genetic Background of the Host

Abstract

G A A b st ra ct s manner with significant inhibition noted at 5.0 and 10.0 μM. 18β-GA washout restored a normal rate of cell migration. No inhibition of migration was noted between 0.625 to 2.5 μM despite reaching near complete inhibition (90-95%) of GJIC at these concentrations. The Cx-43 polypeptide exists in three isoforms under control conditions: two predominant phosphorylated forms (P2 and P1) and one minor non-phosphorylated form (P0). 18β-GA shifts the phosphorylation state of Cx-43 from nearly equal amounts of P2 and P1 to a predominantly P0 isoform at concentrations between 0.625 to 2.5 μM. Confocal microscopy revealed that Cx-43 is not present at the leading-edge lamellipodia extensions of migrating cells, but localizes primarily to the retracting edge at points of contact between cells and along lines of cortical actin filaments. Conclusions: Although a correlation exists between GJIC and Cx-43 phosphorylation state, GJIC and maintenance of the P2 isoform are not required for IEC-6 migration. Based on the specific subcellular localization of Cx-43 in migrating cells, we speculate that regulation of actin cytoskeleton dynamics may be a novel function for gap junction proteins and might regulate epithelial cell migration In Vivo along the intestinal villous. (Supported by an Intramural Research Grant for New Faculty from Michigan State University).