Loss of mitochondrial transmembrane potential and glutathione depletion are not sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in human leukemia K562 cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F15%3A73585330" target="_blank" >RIV/61989592:15110/15:73585330 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0009279715300077" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279715300077</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2015.06.033" target="_blank" >10.1016/j.cbi.2015.06.033</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Loss of mitochondrial transmembrane potential and glutathione depletion are not sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in human leukemia K562 cells

Popis výsledku v původním jazyce

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), an uncoupler of mitochondrial oxidative phosphorylation, inhibits cell proliferation and induces cell death with apoptotic features. It was reported that the cytotoxic effects of FCCP are preceded by a rapid lutathione (GSH) depletion with a subsequent loss of mitochondrial transmembrane potential (DW). The GSH depletion was suggested as the cause of apoptosis in FCCP treated cells. This conclusion was further supported by the finding that all adverse effects of FCCP including cell death can be prevented by N-acetylcysteine (NAC) a precursor of GSH syn-thesis (Han and Park, 2011). Here, we argue that neither loss of DW nor GSH depletion is sufficient to account for induction of apop-tosis in FCCP treated leukemia K562 cells. Indeed, the lowest ncentration of FCCP that brings about the permanent loss of DW and the extensive decrease in GSH level induces cell death in minor population of cells. Only much higher concentrations of FCCP, that exceed the range to achieve permanent collapse of DW , induce extensive apoptosis. The low proapoptotic activity of FCCP could be explained by hyperacti-vation of protein kinase B/Akt. A detailed LC/MS/MS analysis of cell extracts revealed extensive formation of FCCP adducts with GSH. This effect could explain the mechanism of GSH depletion, hich is currently unknown. Although NAC induces an increase in the GSH pool, this effect is not crucial for abrogation of FCCP cytotoxicity. Indeed, the presence of NAC in the growth medium causes a rapid clearance of FCCP due to its quantita-tive conversion into the FCCP–NAC adduct, which is the real cause of abrogated FCCP cytotoxicity.

Název v anglickém jazyce

Loss of mitochondrial transmembrane potential and glutathione depletion are not sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in human leukemia K562 cells

Popis výsledku anglicky

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), an uncoupler of mitochondrial oxidative phosphorylation, inhibits cell proliferation and induces cell death with apoptotic features. It was reported that the cytotoxic effects of FCCP are preceded by a rapid lutathione (GSH) depletion with a subsequent loss of mitochondrial transmembrane potential (DW). The GSH depletion was suggested as the cause of apoptosis in FCCP treated cells. This conclusion was further supported by the finding that all adverse effects of FCCP including cell death can be prevented by N-acetylcysteine (NAC) a precursor of GSH syn-thesis (Han and Park, 2011). Here, we argue that neither loss of DW nor GSH depletion is sufficient to account for induction of apop-tosis in FCCP treated leukemia K562 cells. Indeed, the lowest ncentration of FCCP that brings about the permanent loss of DW and the extensive decrease in GSH level induces cell death in minor population of cells. Only much higher concentrations of FCCP, that exceed the range to achieve permanent collapse of DW , induce extensive apoptosis. The low proapoptotic activity of FCCP could be explained by hyperacti-vation of protein kinase B/Akt. A detailed LC/MS/MS analysis of cell extracts revealed extensive formation of FCCP adducts with GSH. This effect could explain the mechanism of GSH depletion, hich is currently unknown. Although NAC induces an increase in the GSH pool, this effect is not crucial for abrogation of FCCP cytotoxicity. Indeed, the presence of NAC in the growth medium causes a rapid clearance of FCCP due to its quantita-tive conversion into the FCCP–NAC adduct, which is the real cause of abrogated FCCP cytotoxicity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10609 - Biochemical research methods

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

—

Svazek periodika

2015

Číslo periodika v rámci svazku

5. září 2015

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

11

Strana od-do

100-110

Kód UT WoS článku

000361405600011

EID výsledku v databázi Scopus

2-s2.0-84947475113