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@article{1320663,
author = {Kučera, Jan and Binó, Lucia and Štefková, Kateřina and Jaroš, Josef and Vašíček, Ondřej and Večeřa, Josef and Kubala, Lukáš and Pacherník, Jiří},
article_number = {7409196},
doi = {http://dx.doi.org/10.1155/2016/7409196},
keywords = {NADPH OXIDASE INHIBITOR; SMOOTH-MUSCLE-CELLS; WNT-BETA-CATENIN; REACTIVE OXYGEN; SELF-RENEWAL; CARDIOMYOCYTE DIFFERENTIATION; INTRACELLULAR SUPEROXIDE; ENDOTHELIAL-CELLS; REDOX-REGULATION; FREE-RADICALS},
language = {eng},
issn = {1942-0900},
journal = {Oxidative Medicine and Cellular Longevity},
title = {Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells},
volume = {2016},
year = {2016}
}
TY - JOUR
ID - 1320663
AU - Kučera, Jan - Binó, Lucia - Štefková, Kateřina - Jaroš, Josef - Vašíček, Ondřej - Večeřa, Josef - Kubala, Lukáš - Pacherník, Jiří
PY - 2016
TI - Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells
JF - Oxidative Medicine and Cellular Longevity
VL - 2016
IS - 7409196
SP - 1-14
EP - 1-14
PB - Hindawi Publishing Corporation
SN - 19420900
KW - NADPH OXIDASE INHIBITOR
KW - SMOOTH-MUSCLE-CELLS
KW - WNT-BETA-CATENIN
KW - REACTIVE OXYGEN
KW - SELF-RENEWAL
KW - CARDIOMYOCYTE DIFFERENTIATION
KW - INTRACELLULAR SUPEROXIDE
KW - ENDOTHELIAL-CELLS
KW - REDOX-REGULATION
KW - FREE-RADICALS
N2 - Reactive oxygen species (ROS) are important regulators of cellular functions. In embryonic stem cells, ROS are suggested to influence differentiation status. Regulated ROS formation is catalyzed primarily by NADPH-dependent oxidases (NOXs). Apocynin and diphenyleneiodonium are frequently used inhibitors of NOXs; however, both exhibit uncharacterized effects not related to NOXs inhibition. Interestingly, in our model of mouse embryonic stem cells we demonstrate low expression of NOXs. Therefore we aimed to clarify potential side effects of these drugs. Both apocynin and diphenyleneiodonium impaired proliferation of cells. Surprisingly, we observed prooxidant activity of these drugs determined by hydroethidine. Further, we revealed that apocynin inhibits PI3K/Akt pathway with its downstream transcriptional factor Nanog. Opposite to this, apocynin augmented activity of canonical Wnt signaling. On the contrary, diphenyleneiodonium activated both PI3K/Akt and Erk signaling pathways without affecting Wnt. Our data indicates limits and possible unexpected interactions of NOXs inhibitors with intracellular signaling pathways.
ER -
KUČERA, Jan, Lucia BINÓ, Kateřina ŠTEFKOVÁ, Josef JAROŠ, Ondřej VAŠÍČEK, Josef VEČEŘA, Lukáš KUBALA a Jiří PACHERNÍK. Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells. \textit{Oxidative Medicine and Cellular Longevity}. Hindawi Publishing Corporation, roč.~2016, č.~7409196, s.~1-14. ISSN~1942-0900. doi:10.1155/2016/7409196. 2016.
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