Complestatin, a bicyclo hexapeptide from Streptomyces, was isolated as a possible regulator of neuronal cell death. In this study, we report an anti-apoptotic activity of complestatin and its underlying molecular mechanism. Complestatin blocked TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis and activation of caspase-3 and -8 at micromolar concentration levels without inhibiting the catalytic activities of these caspases. Complestatin potently induced a rapid and sustained AKT/PKB activation and Bad phosphorylation, resulting in inhibition of mitochondrial cytochrome c release. These anti-apoptotic activities of complestatin were significantly abrogated in cells expressing dominant negative AKT/PKB. Taken together, our results suggest that complestatin prevents apoptotic cell death via AKT/PKB-dependent inhibition of the mitochondrial apoptosis signal pathway. The novel property of complestatin may be valuable for developing new pharmaceutical means that will control unwanted cell death.
|Number of pages||12|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2004 Jan 2|
Bibliographical noteFunding Information:
We extend our sincere thanks to Dr. Timothy R. Billiar (University of Pittsburgh) for providing HA-AKT and DN-AKT expression vector. We thank Dr. James A. Bibb (University of Texas Southwestern) for critical reading of the manuscript. This work was supported by G7 and NRL grants (to I.-D.Y.) and a Vascular System Research Center grant (to Y.-G.K.), Ministry of Science and Technology, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology