Inhibitory effects of a tryptamine derivative on ultraviolet radiation-induced apoptosis in MC3T3-E1 mouse osteoblasts

J Pharmacol Sci. 2011;115(2):214-20. doi: 10.1254/jphs.10208fp. Epub 2011 Jan 26.

Abstract

MS-IPA1 is a new synthetic compound that is synthesized from tryptamine. Recently, our group demonstrated that SST-VED-I-1, which has a similar chemical structure to MS-IPA1, inhibits starvation-induced apoptosis in osteoblasts. However, the effects of MS-IPA1 on apoptosis in osteoblasts have not yet been examined. Therefore, this study examined the effects of this compound on apoptosis in osteoblasts. In this study, MC3T3-E1 mouse osteoblasts were used and apoptosis was induced by ultraviolet radiation (UV). We investigated the effect of MS-IPA1 on apoptosis by analyzing caspase3/7 activity, translocation of phosphatidylserine (PS), and mRNA expression levels of Bcl-2 and Bax. In addition, it was investigated whether MS-IPA1 affects cell proliferation and cell cycle progression. We found that MS-IPA1 had no effect on cell proliferation or cell cycle progression. However, MS-IPA1 suppressed UV-induced cell death in a dose-dependent manner, which was accompanied with the inhibition of caspase activation and translocation of PS. Furthermore, after UV exposure, Bcl-2 expression was increased in the MS-IPA1-treated cells as compared to that in the vehicle-treated cells. In contrast, Bax expression was decreased in the MS-IPA1-treated cell as compared to that in the vehicle-treated cells. These results suggest that MS-IPA1 has an inhibitory effect on apoptosis in osteoblasts through a Bcl-2 family-dependent signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexins / metabolism
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / radiation effects
  • Signal Transduction / drug effects
  • Tryptamines / pharmacology*
  • Ultraviolet Rays*

Substances

  • 1-hydroxy-N-methoxycarbonyltryptamine
  • Annexins
  • Tryptamines
  • Caspase 3