alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F10%3A%230000624" target="_blank" >RIV/00027162:_____/10:#0000624 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/10:00349091

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

Popis výsledku v původním jazyce

Mitocans are drugs selectively killing cancer cells by destabilizing mitochondria and generate reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to alpha-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types tested. Bak forms high molecular weight complexes in the mitochondria upon alfa-TOS treatment. We conclude that the major events induced by alpha-TOS in cancer cells downstream ofROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS.

Název v anglickém jazyce

alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

Popis výsledku anglicky

Mitocans are drugs selectively killing cancer cells by destabilizing mitochondria and generate reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to alpha-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types tested. Bak forms high molecular weight complexes in the mitochondria upon alfa-TOS treatment. We conclude that the major events induced by alpha-TOS in cancer cells downstream ofROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Apoptosis

ISSN

1360-8185

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

000279190700003

EID výsledku v databázi Scopus

—