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Chlorpromazine, a tranquilizing agent for treatments of psychiatric disorders, mimics hypotonic stress and causes membrane deformation. Application of 10 \u00b5g\/ml of chlorpromazine suppressed BSP mRNA levels after 12 and 24 h in osteoblast\u2010like ROS17\/2.8 cells and rat stromal bone marrow cells (SBMC\u2010D8). Chlorpromazine (10 \u00b5g\/ml) decreased luciferase activity of the construct (pLUC3; \u2212116 to +60 of the rat BSP gene promoter) after 12 h, the effect was inhibited by the tyrosine kinase inhibitor herbimycin A (HA) and MAP kinase kinase inhibitor U0126. Introduction of 2\u2010bp mutation in the pLUC3 construct showed that the chlorpromazine effects were mediated by cAMP response element (CRE) and FGF2 response element (FRE). In gel shift assays, using radiolabeled double\u2010stranded CRE and FRE oligonucleotides, which revealed decreased binding of nuclear proteins from chlorpromazine\u2010stimulated cells. These studies, therefore, show that chlorpromazine suppresses BSP gene transcription through tyrosine and MAP kinases\u2010dependent pathways and that the chlorpromazine effects are mediated by CRE and FRE elements in the proximal promoter of the <jats:italic>BSP<\/jats:italic> gene. J. Cell. Biochem. 97: 1198\u20131206, 2006. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20706","type":"journal-article","created":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T17:46:29Z","timestamp":1132249589000},"page":"1198-1206","source":"Crossref","is-referenced-by-count":3,"title":["Effect of chlorpromazine on bone sialoprotein (BSP) gene 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