Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells

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Authors

KUČERA Jan BINÓ Lucia ŠTEFKOVÁ Kateřina JAROŠ Josef VAŠÍČEK Ondřej VEČEŘA Josef KUBALA Lukáš PACHERNÍK Jiří

Year of publication 2016
Type Article in Periodical
Magazine / Source Oxidative Medicine and Cellular Longevity
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1155/2016/7409196
Field Genetics and molecular biology
Keywords NADPH OXIDASE INHIBITOR; SMOOTH-MUSCLE-CELLS; WNT-BETA-CATENIN; REACTIVE OXYGEN; SELF-RENEWAL; CARDIOMYOCYTE DIFFERENTIATION; INTRACELLULAR SUPEROXIDE; ENDOTHELIAL-CELLS; REDOX-REGULATION; FREE-RADICALS
Description 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.
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