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

0471984 - BFÚ 2017 RIV US eng J - Journal Article
Kučera, J. - Binó, Lucia - Štefková, K. - Jaros, J. - Vašíček, Ondřej - Veceřa, J. - Kubala, Lukáš - Pachernik, J.
Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells.
Oxidative Medicine and Cellular Longevity. Roč. 2016, č.2016 (2016), č. článku 7409196. ISSN 1942-0900. E-ISSN 1942-0994
Institutional support: RVO:68081707
Keywords : nadph oxidase inhibitor * smooth-muscle-cells * wnt-beta-catenin
Subject RIV: BO - Biophysics
Impact factor: 4.593, year: 2016

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.
Permanent Link: http://hdl.handle.net/11104/0269343