title: The effects of 2-aminoethoxydiphenyl borate and diphenylboronic anhydride on gap junctions composed of Connexin43 in TM₄ sertoli cells.
abstract: 2-Aminoethoxydiphenyl borate (2-APB) has recently been demonstrated to inhibit gap junction (GJ) channels, whereas the underlying mechanisms are still unknown. Using mouse TM₄ Sertoli cell which expresses connexin43 (Cx43), we explored the effects of 2-APB and its analogues on dye-coupling through junctional channels formed by Cx43 and on expression of Cx43. Exposure of the cells to 2-APB (1-50 µM) and one of its analogues diphenylboronic anhydride (DPBA) (1-30 µM) for 4 h leads to a significant decrease in dye coupling of GJ in a concentration-dependent manner. The inhibitory effects of 2-APB and DPBA are reversible since decreased GJ coupling resumes after the two compounds are washed out. The disfunction of GJ induced by 2-APB and DPBA is associated with a decrease in total amount of Cx43 protein and number of GJs on the cell membrane. 2-APB and DPBA do not alter Cx43 phosphorylation state and the level of Cx43 mRNA expression. The loss of Cx43 protein is prevented by either lysosomal or proteasomal inhibitor, suggesting that the decrease in Cx43 results from a 2-APB or DPBA-enhanced degradation of Cx43. The present results indicate that 2-APB and DPBA inhibit GJ communication through decreasing Cx43 expression in TM₄ cells.
authors: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, China.
authors: Yan
authors: Y
authors: Yang
authors: Ming-Hui
authors: MH
authors: Cao
authors: Qin
authors: Q
authors: Wang
authors: Dong-Dong
authors: DD
authors: Yuan
authors: Li
authors: L
authors: Li
authors: Liang
authors: L
authors: Tao
mesh_terms: D000812:Anhydrides / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001896:Boron Compounds / Q000494:pharmacology*; D002460:Cell Line; D018031:Connexin 43 / Q000187:drug effects*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects*; D008297:Male; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects*
chemical_list: D000812:Anhydrides; D001896:Boron Compounds; D018031:Connexin 43; D017931:DNA Primers; C044960:diphenylborinic acid; C109986:2-aminoethoxydiphenyl borate