title: Cardiotonic steroid ouabain stimulates expression of blood-testis barrier proteins claudin-1 and -11 and formation of tight junctions in Sertoli cells.
abstract: The interaction of ouabain with the sodium pump induces signalling cascades resembling those triggered by hormone/receptor interactions. In the rat Sertoli cell line 93RS2, ouabain at low concentrations stimulates the c-Src/c-Raf/Erk1/2 signalling cascade via its interaction with the α4 isoform of the sodium pump expressed in these cells, leading to the activation of the transcription factor CREB. As a result of this signalling sequence, ouabain stimulates expression of claudin-1 and claudin-11, which are also controlled by a CRE promoter. Both of these proteins are known to be essential constituents of tight junctions (TJ) between Sertoli cells, and as a result of the ouabain-induced signalling TJ formation between neighbouring Sertoli cells is significantly enhanced by the steroid. Thus, ouabain-treated cell monolayers display higher transepithelial resistance and reduced free diffusion of FITC-coupled dextran in tracer diffusion assays. Taking into consideration that the formation of TJ is indispensable for the maintenance of the blood-testis barrier (BTB) and therefore for male fertility, the actions of ouabain described here and the fact that this and other related cardiotonic steroids (CTS) are produced endogenously suggest a direct influence of ouabain/sodium pump interactions on the maintenance of the BTB and thereby an effect on male fertility. Since claudin-1 and claudin-11 are also present in other blood-tissue barriers, one can speculate that ouabain and perhaps other CTS influence the dynamics of these barriers as well.
authors: Institut für Veterinär-Physiologie und -Biochemie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, Giessen, Germany.
authors: Raimund
authors: R
authors: Dietze
authors: Institut für Veterinär-Physiologie und -Biochemie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, Giessen, Germany.
authors: Mazen
authors: M
authors: Shihan
authors: Zentrum f. Frauenheilkunde und Geburtshilfe, Justus-Liebig-Universität, Giessen, Germany; Institut f. Anatomie und Zellbiologie, Fachbereich Medizin, Justus-Liebig-Universität, Giessen, Germany.
authors: Angelika
authors: A
authors: Stammler
authors: Zentrum f. Frauenheilkunde und Geburtshilfe, Justus-Liebig-Universität, Giessen, Germany.
authors: Lutz
authors: L
authors: Konrad
authors: Institut für Veterinär-Physiologie und -Biochemie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, Giessen, Germany. Electronic address: Georgios.Scheiner-Bobis@vetmed.uni-giessen.de.
authors: Georgios
authors: G
authors: Scheiner-Bobis
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000166:cytology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D002316:Cardiotonic Agents; D062445:Claudin-1; D057167:Claudins; C568114:Cldn1 protein, rat; C492353:Cldn11 protein, rat; D010042:Ouabain
keywords: Claudin-1; Claudin-11; Ouabain; Sertoli cells; Tight junction