Воздействие оксихинолина изменяет экспрессию генов клаудинов, что снижает барьерную функцию монослоя клеток BeWo b30
The hypoxic response critically depends on the rapid stabilization of the Hypoxia-Inducible Factor (HIF). In normoxic conditions, HIF-prolyl hydroxylases mark α-subunits of HIF for degradation, while the hypoxia results in stabilization of HIF-α. Oxyquinoline derivatives suppress the activity of HIF-prolyl hydroxylases, leading to the stabilization of HIF. Here we show that the 24 hour incubation of the trophoblast model choriocarcinoma cells BeWo b30 line with the oxyquinoline derivative leads to a decrease in the transepithelial electrical resistance (TEER) of the cell monolayer, while the permeability of the monolayer for the FITC-dextran (70 kDa) remains unchanged. These observations indicate that the overall barrier function remain preserved, while the structure of intercellular tight junctions may undergo remodeling. Using Affymetrix Human Transcriptome Array 2.0, we show that the treatment with oxyquinoline derivative lead to a decrease in the expression of claudines 6 and 7 (CLDN6, CLDN7), occludin (OCLN), contact adhesion molecule 3 (JAM3) and angiotomin-like protein 1 (AMOTL1), which possibly explain the observed changes in TEER.