Effect of chlorpromazine on bone sialoprotein (BSP) gene transcription

Yu Nakajima, Naoko Kato, Youhei Nakayama, Dong Soon Kim, Hideki Takai, Masato Arai, Ryoichiro Saito, Hiroshi Samoto, Emi Shimizu, Yorimasa Ogata

Research output: Contribution to journalArticle

Abstract

Bone sialoprotein (BSP), an early marker of osteoblast differentiation. Whereas physical forces may play an important role in the regulation of bone cell function, little is known about how cells are able to sense mechanical loads. Chlorpromazine, a tranquilizing agent for treatments of psychiatric disorders, mimics hypotonic stress and causes membrane deformation. Application of 10 μg/ml of chlorpromazine suppressed BSP mRNA levels after 12 and 24 h in osteoblast-like ROS 17/2.8 cells and rat stromal bone marrow cells (SBMC-D8). Chlorpromazine (10 μg/ml) decreased luciferase activity of the construct (pLUC3;-116 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-bp 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-stranded CRE and FRE oligonucleotides, which revealed decreased binding of nuclear proteins from chlorpromazine-stimulated cells. These studies, therefore, show that chlorpromazine suppresses BSP gene transcription through tyrosine and MAP kinases-dependent pathways and that the chlorpromazine effects are mediated by CRE and FRE elements in the proximal promoter of the BSP gene.

Original languageEnglish (US)
Pages (from-to)1198-1206
Number of pages9
JournalJournal of Cellular Biochemistry
Volume97
Issue number6
DOIs
StatePublished - Apr 15 2006

Keywords

  • Bone sialoprotein
  • Chlorpromazine
  • Gene regulation
  • Hypotonic stress
  • Mineralized tissues
  • Osteoblasts
  • Stromal bone marrow cell
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Nakajima, Y., Kato, N., Nakayama, Y., Kim, D. S., Takai, H., Arai, M., Saito, R., Samoto, H., Shimizu, E., & Ogata, Y. (2006). Effect of chlorpromazine on bone sialoprotein (BSP) gene transcription. Journal of Cellular Biochemistry, 97(6), 1198-1206. https://doi.org/10.1002/jcb.20706