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Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels
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SYSNO ASEP 0349091 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels Author(s) Procházka, L. (CZ)
Dong, L.F. (AU)
Vališ, Karel (BTO-N)
Freeman, R. (AU)
Ralph, S.J. (AU)
Turánek, J. (CZ)
Neužil, Jiří (BTO-N) RIDSource Title Apoptosis. - : Springer - ISSN 1360-8185
Roč. 15, č. 7 (2010), s. 782-794Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords Vitamin E succinate ; apoptosis ; Noxa-Bak Subject RIV EB - Genetics ; Molecular Biology R&D Projects KAN200520703 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) IAA500520702 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) IAA500520602 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000279190700003 DOI 10.1007/s10495-010-0482-z Annotation Many mitocans selectively killing cancer cells by destabilizing mitochondria induce apoptosis via generation of reactive oxygen species. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in this mechanism has been determined. Exposure of several different cancer cell lines to alpha-TOS increased expression of the Noxa protein, independently of the cellular p53 status. alpha-TOS caused a profound conformational change in the Bak protein in all cell types, in the Bax protein only in non-small cell lung cancer cells. Immunoprecipitation studies indicated activation of Bak or Bax proteins to form high molecular weight complexes. RNAi knockdown revealed that Noxa and Bak are required for alpha-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. Then, the events induced by alpha-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2011
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