Knyazev E N, Petrov V A, Gazizov I N, Gerasimenko T N, Tsypina I M, Tonevitsky A G, Sukhikh G T
BioClinicum Research Center, Moscow, Russia.
National Research University Higher School of Economics, Moscow, Russia.
Bull Exp Biol Med. 2019 Jan;166(3):369-372. doi: 10.1007/s10517-019-04352-z. Epub 2019 Jan 9.
Natural response to hypoxia critically depends on rapid stabilization of hypoxia-inducible factor (HIF). Under normoxic conditions, HIF-prolyl hydroxylases mark α-subunits of HIF for degradation, while hypoxia results in stabilization of HIF-α. Oxyquinoline derivatives suppress activity of HIF-prolyl hydroxylases leading to HIF activation in the cell. Here we show that 24-h incubation of BeWo b30 choriocarcinoma cells (a model of trophoblast in the placental barrier) with oxyquinoline derivative leads to a decrease in transepithelial electrical resistance (TEER) of the cell monolayer, while the permeability of the monolayer for FITC-dextran (70 kDa) remains unchanged. These findings suggest that the overall barrier function is preserved, while the structure of intercellular tight junctions can undergo minor changes. Using Affymetrix Human Transcriptome Array 2.0, we showed that the treatment with oxyquinoline derivative was followed by a decrease in the expression of claudins 6 and 7 (CLDN6, CLDN7), occludin (OCLN), contact adhesion molecule 3 (JAM3), and angiomotinlike protein 1 (AMOTL1).
对缺氧的自然反应关键取决于缺氧诱导因子（HIF）的快速稳定。在常氧条件下，HIF脯氨酰羟化酶标记HIF的α亚基以便降解，而缺氧会导致HIF-α的稳定。氧喹啉衍生物抑制HIF脯氨酰羟化酶的活性，从而导致细胞内HIF激活。在此我们表明，用氧喹啉衍生物对BeWo b30绒毛膜癌细胞（胎盘屏障中滋养层细胞的模型）进行24小时孵育会导致细胞单层的跨上皮电阻（TEER）降低，而单层对异硫氰酸荧光素标记的葡聚糖（70 kDa）的通透性保持不变。这些发现表明，整体屏障功能得以保留，而细胞间紧密连接的结构可能会发生轻微变化。使用Affymetrix人类转录组阵列2.0，我们发现用氧喹啉衍生物处理后，闭合蛋白6和7（CLDN6、CLDN7）、闭合蛋白（OCLN）、接触粘附分子3（JAM3）和血管动蛋白样蛋白1（AMOTL1）的表达会降低。
