Complestatin prevents apoptotic cell death: Inhibition of a mitochondrial caspase pathway through AKT/PKB activation

Eok Cheon Kim, Bong Sik Yun, In Ja Ryoo, Jeong Ki Min, Moo Ho Won, Kwang Soon Lee, Young Myeong Kim, Ick Dong Yoo, Young-Guen Kwon

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalBiochemical and Biophysical Research Communications
Volume313
Issue number1
DOIs
Publication statusPublished - 2004 Jan 2

Fingerprint

Cell death
Caspases
Cell Death
Chemical activation
TNF-Related Apoptosis-Inducing Ligand
Apoptosis
Phosphorylation
Caspase 8
Streptomyces
Cytochromes c
complestatin
Caspase 3
Signal Transduction
Catalyst activity
Cells
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, Eok Cheon ; Yun, Bong Sik ; Ryoo, In Ja ; Min, Jeong Ki ; Won, Moo Ho ; Lee, Kwang Soon ; Kim, Young Myeong ; Yoo, Ick Dong ; Kwon, Young-Guen. / Complestatin prevents apoptotic cell death : Inhibition of a mitochondrial caspase pathway through AKT/PKB activation. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 313, No. 1. pp. 193-204.
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Complestatin prevents apoptotic cell death : Inhibition of a mitochondrial caspase pathway through AKT/PKB activation. / Kim, Eok Cheon; Yun, Bong Sik; Ryoo, In Ja; Min, Jeong Ki; Won, Moo Ho; Lee, Kwang Soon; Kim, Young Myeong; Yoo, Ick Dong; Kwon, Young-Guen.

In: Biochemical and Biophysical Research Communications, Vol. 313, No. 1, 02.01.2004, p. 193-204.

Research output: Contribution to journalArticle

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AU - Kim, Eok Cheon

AU - Yun, Bong Sik

AU - Ryoo, In Ja

AU - Min, Jeong Ki

AU - Won, Moo Ho

AU - Lee, Kwang Soon

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