Ichikawa Akira, Tsuchiya Toshie
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
J Biomed Mater Res. 2002 Nov;62(2):157-62. doi: 10.1002/jbm.10239.
Gap junctional intercellular communication (GJIC) is inhibited by 4,4'-di(ethoxycarboamide) diphenylmethane (MDU) and polytetramethylene oxide 1000 (PTMO1000), which are model chemicals of hard and soft segments of polyetherurethane (PEU), respectively. In our previous study, we suggested that the inhibition of GJIC induced by MDU and PTMO1000 may lead to accelerate promotion step by both segments after the initiation step by hard segment, MDU. To examine this hypothesis, we established connexin 43 overexpressed clones from Balb/c 3T3 A31-1-1 clones (A31-1-1 cells) by transfection. Here we show that these clones acquired much higher GJIC ability than parental A31-1-1 cells and kept them even if MDU or PTMO1000 was added to the culture. We also found that Mutation of Cx43 at Tyr-265 resulted in reduced inhibition of GJIC induced by MDU and PTMO1000. These findings suggest that inhibition of GJIC by PEU may be caused by Tyr-265 phosphorylation of Cx43 molecule.
间隙连接细胞间通讯（GJIC）受到4,4'-二（乙氧羰基酰胺）二苯甲烷（MDU）和聚四亚甲基醚1000（PTMO1000）的抑制，它们分别是聚醚聚氨酯（PEU）硬段和软段的模型化合物。在我们之前的研究中，我们提出MDU和PTMO1000诱导的GJIC抑制可能导致在硬段MDU引发步骤之后，两个链段加速促进步骤。为了检验这一假设，我们通过转染从Balb/c 3T3 A31-1-1克隆（A31-1-1细胞）建立了连接蛋白43过表达克隆。在此我们表明，这些克隆获得了比亲代A31-1-1细胞更高的GJIC能力，并且即使在培养物中加入MDU或PTMO1000也能保持这种能力。我们还发现，Cx43在Tyr-265处的突变导致MDU和PTMO1000诱导的GJIC抑制作用减弱。这些发现表明，PEU对GJIC的抑制可能是由Cx43分子的Tyr-265磷酸化引起的。
