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

Oxidative Medicine and Cellular Longevity
Jan KučeraJiří Pacherník

Abstract

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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Citations

May 21, 2019·The Korean Journal of Parasitology·Pu Reum SunGuang-Ho Cha
Dec 13, 2019·Antioxidants & Redox Signaling·Mathieu Chocry, Ludovic Leloup
Apr 7, 2020·Current Pharmaceutical Design·Joanna WieczfinskaRafal Pawliczak
Dec 22, 2020·Electromagnetic Biology and Medicine·María Antonia MartínezMaría Ángeles Trillo
Jan 10, 2021·International Journal of Molecular Sciences·Kateřina SkopalováPetr Humpolíček
Jul 3, 2021·Antioxidants·Tullia MaraldiSilvana Hrelia
Oct 1, 2021·Journal of Thrombosis and Haemostasis : JTH·Kamil PrzyborowskiStefan Chlopicki

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Methods Mentioned

BETA
protein assay
fluorescence microscopy
Transfection
PCR

Software Mentioned

R Statistics Integration
CellProfiler

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