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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/GA17-01813S" target="_blank" >GA17-01813S: Redox signaling by mitochondrial reactive oxygen species</a><br>

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Biochimica Et Biophysica Acta-Bioenergetics

ISSN

0005-2728

e-ISSN

—

Volume of the periodical

1858

Issue of the periodical within the volume

9

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

750-762

UT code for WoS article

000407523500003

EID of the result in the Scopus database

2-s2.0-85021392753