Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00482786" target="_blank" >RIV/67985823:_____/17:00482786 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bbabio.2017.05.005" target="_blank" >http://dx.doi.org/10.1016/j.bbabio.2017.05.005</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbabio.2017.05.005" target="_blank" >10.1016/j.bbabio.2017.05.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation

Popis výsledku v původním jazyce

Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion pairing of cationic SkQl(+) with free fatty acid anions resulting in uncoupling, ii) SkQ1H(2) ability to interact with lipoperoxyl radical, interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Q(i)), involving the reduction of SkQ1 to SkQ1H(2) by ubiquinol. We elucidated SkQl antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (J(m)) and cytosolic H2O2 (J(c)) release rates in HepG2 cells. Only in glycolytic cells, SkQl prevented the rotenone-induced enhancement of Jm and Jc but not basal releases without rotenone. The effect ceased in glutaminolytic aglycemic cells, in which the redox parameter NAD(P)H/FAD increased after rotenone in contrast to its decrease in glycolytic cells. Autofluorescence decay indicated decreased NADPH/NADH ratios with rotenone in both metabolic modes. SkQl did not increase cell respiration and diminished Jm established high by antimycin or myxothiazol but not by stigmatellin. The revealed SkQ1 antioxidant modes reflect its reduction to SkQ1H(2) at Complex I I-Q or Complex III Q(i) site. Both reductions diminish electron diversions to oxygen thus attenuating superoxide formation. Resulting SkQ1H(2) oxidizes back to SkQ1at the second (flavin) Complex I site, previously indicated for MitoQ(10). Regeneration proceeds only at lower NAD(P)H/FAD in glycolytic cells. In contrast, cyclic SkQ1 reduction/SkQ1H(2) oxidation does not substantiate antioxidant activity in intact cells in the absence of oxidative stress (neither pro-oxidant activity, representing a great advantage). A targeted delivery to oxidative-stressed tissues is suggested for the effective antioxidant therapy based on SkQ1.

Název v anglickém jazyce

Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation

Popis výsledku anglicky

Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion pairing of cationic SkQl(+) with free fatty acid anions resulting in uncoupling, ii) SkQ1H(2) ability to interact with lipoperoxyl radical, interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Q(i)), involving the reduction of SkQ1 to SkQ1H(2) by ubiquinol. We elucidated SkQl antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (J(m)) and cytosolic H2O2 (J(c)) release rates in HepG2 cells. Only in glycolytic cells, SkQl prevented the rotenone-induced enhancement of Jm and Jc but not basal releases without rotenone. The effect ceased in glutaminolytic aglycemic cells, in which the redox parameter NAD(P)H/FAD increased after rotenone in contrast to its decrease in glycolytic cells. Autofluorescence decay indicated decreased NADPH/NADH ratios with rotenone in both metabolic modes. SkQl did not increase cell respiration and diminished Jm established high by antimycin or myxothiazol but not by stigmatellin. The revealed SkQ1 antioxidant modes reflect its reduction to SkQ1H(2) at Complex I I-Q or Complex III Q(i) site. Both reductions diminish electron diversions to oxygen thus attenuating superoxide formation. Resulting SkQ1H(2) oxidizes back to SkQ1at the second (flavin) Complex I site, previously indicated for MitoQ(10). Regeneration proceeds only at lower NAD(P)H/FAD in glycolytic cells. In contrast, cyclic SkQ1 reduction/SkQ1H(2) oxidation does not substantiate antioxidant activity in intact cells in the absence of oxidative stress (neither pro-oxidant activity, representing a great advantage). A targeted delivery to oxidative-stressed tissues is suggested for the effective antioxidant therapy based on SkQ1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/GA17-01813S" target="_blank" >GA17-01813S: Redoxní signalizace pomocí mitochondriálních reaktivních forem kyslíku</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Biochimica Et Biophysica Acta-Bioenergetics

ISSN

0005-2728

e-ISSN

—

Svazek periodika

1858

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

750-762

Kód UT WoS článku

000407523500003

EID výsledku v databázi Scopus

2-s2.0-85021392753