Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells
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.
References
Citations
Surfactin induces autophagy, apoptosis, and cell cycle arrest in human oral squamous cell carcinoma.
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Autophagy & Aging: Inhibitors
The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.
Adult Stem Cells
Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.
AKT Pathway
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.
Cardiac Regeneration
Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.
Cardiovascular Homeostasis
Cardiovascular regulation and homeostasis is important in maintaining health and dysfunction may lead to cardiovascular diseases. Nitric oxide and vascular endothelium are one of many molecules involved in the homeostatic mechanism. Here is the latest research on cardiovascular homeostasis.