ArticlePloS one2014
The redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Voluntary running exercise is associated with metabolic shifts linked to adult hippocampal neurogenesis.Scientific reports · 2026Article
- From DNA Repair to Redox Signaling: The Multifaceted Role of APEX1 (Apurinic/Apyrimidinic Endonuclease 1) in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- APEX1 Nuclease and Redox Functions are Both Essential for Adult Mouse Hematopoietic Stem and Progenitor Cells.Stem cell reviews and reports · 2023Article
- Article
- Redox-Dependent Modulation of Human Liver Progenitor Cell Line Fate.International journal of molecular sciences · 2023Article
- A Novel HypomorphicAntioxidants & redox signaling · 2023Article
- α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.Progress in neurobiology · 2022Article
- APE1/Ref-1 Role in Inflammation and Immune Response.Frontiers in immunology · 2022Review
- NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function.Antioxidants (Basel, Switzerland) · 2021Review
- The FOXO signaling axis displays conjoined functions in redox homeostasis and stemness.Free radical biology & medicine · 2021Review
- Human Adipose-Derived Stem Cells in Madelung's Disease: Morphological and Functional Characterization.Cells · 2020Article
- Review
- Prion protein deficiency impairs hematopoietic stem cell determination and sensitizes myeloid progenitors to irradiation.Haematologica · 2020Article
- Small Maf functions in the maintenance of germline stem cells in the Drosophila testis.Redox biology · 2018Article
- Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation.Oncotarget · 2018Article
- Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with HTranslational neurodegeneration · 2017Article
- Cardiac Cell Senescence and Redox Signaling.Frontiers in cardiovascular medicine · 2017Review
- Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Apoptosis-Resistant Cardiac Progenitor Cells Modified With Apurinic/Apyrimidinic Endonuclease/Redox Factor 1 Gene Overexpression Regulate Cardiac Repair After Myocardial Infarction.Stem cells translational medicine · 2016Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledLow-to-moderate levels of reactive oxygen species (ROS) govern different steps of neurogenesis via molecular pathways that have been decrypted only partially. Although it has been postulated that redox-sensitive molecules are involved in neuronal differentiation, the molecular bases for this process have not been elucidated yet. The aim of this work was therefore to study the role played by the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the differentiation process of human adipose tissue-derived multipotent adult stem cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal phenotype. METHODS AND
resultsApplying a definite protocol, hAT-MASC can adopt a neural fate. During this maturation process, differentiating cells significantly increase their intracellular Reactive Oxygen Species (ROS) levels and increase the APE1 nuclear fraction bound to chromatin. This latter event is paralleled by the increase of nuclear NF-κB, a transcription factor regulated by APE1 in a redox-dependent fashion. Importantly, the addition of the antioxidant N-acetyl cysteine (NAC) to the differentiation medium partially prevents the nuclear accumulation of APE1, increasing the neuronal differentiation of hAT-MASC. To investigate the involvement of APE1 in the differentiation process, we employed E3330, a specific inhibitor of the APE1 redox function. The addition of E3330, either to the neurogenic embryonic carcinoma cell line NT2-D1or to hAT-MASC, increases the differentiation of stem cells towards a neural phenotype, biasing the differentiation towards specific subtypes, such as dopaminergic cells. In conclusion, during the differentiation process of stem cells towards a neuroectodermic phenotype, APE1 is recruited, in a ROS-dependent manner, to the chromatin. This event is associated with an inhibitory effect of APE1 on neurogenesis that may be reversed by E3330. Therefore, E3330 may be employed both to boost neural differentiation and to bias the differentiation potential of stem cells towards specific neuronal subtypes. These findings provide a molecular basis for the redox-mediated hypothesis of neuronal differentiation program.
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