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

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.

• Authors: Yoshikazu Mikami, Motoki Senoo, Mio Lee, Kiyoshi Yamada, Kuniyasu Ochiai, Masaki J Honda, Eri Watanabe, Nobukazu Watanabe, Masanori Somei, Minoru Takagi
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 115 Issue 2 Pg. 214-20 ( 2011) ISSN: 1347-8648 [Electronic] Japan
• PMID: 21282935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, drug effects, radiation effects)
• Signal Transduction (drug effects)
• Tryptamines (pharmacology)
• Ultraviolet Rays