Publication: Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
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Date
2021-09-02
Authors
Caballano-Infantes, Estefanía
Díaz, Irene
Hitos, Ana Belén
Cahuana, Gladys Margot
Martínez-Ruiz, Antonio
Soria-Juan, Bárbara
Rodríguez-Griñolo, Rosario
Hmadcha, Abdelkrim
Martín, Franz
Soria, Bernat
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Abstract
The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1α and HIF-2α) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.
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MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::DEET
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Hydroxylation
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Energy Metabolism::Proton-Motive Force::Membrane Potential, Mitochondrial
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Mitochondrial Turnover::Mitochondrial Dynamics
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Proteasome Endopeptidase Complex
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Oxygen Consumption
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolome
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::Glycolysis
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription Factors
Medical Subject Headings::Anatomy::Cells::Stem Cells::Pluripotent Stem Cells
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric Oxide
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Respiratory::Anoxia
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Hydroxylation
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Proteasome Inhibitors
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::DEET
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Hydroxylation
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Energy Metabolism::Proton-Motive Force::Membrane Potential, Mitochondrial
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Mitochondrial Turnover::Mitochondrial Dynamics
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Proteasome Endopeptidase Complex
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Oxygen Consumption
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolome
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::Glycolysis
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription Factors
Medical Subject Headings::Anatomy::Cells::Stem Cells::Pluripotent Stem Cells
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric Oxide
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Respiratory::Anoxia
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Hydroxylation
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Proteasome Inhibitors
DeCS Terms
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Keywords
Pluripotency, Normoxia, Nitric oxide, Hypoxia, Metabolism, Hydroxylation, Mitochondria, Mitochondrial membranes, Proteasome inhibitor, Oxygen consumption, Glycolysis, Pluripotent stem cells, Óxido nítrico, Hipoxia, Metabolismo, Hidroxilación, Mitocondrias, Membranas mitocondriales, Inhibidores de proteasoma, Consumo de oxígeno, Glucólisis, Células madre pluripotentes
Citation
Caballano-Infantes E, Díaz I, Hitos AB, Cahuana GM, Martínez-Ruiz A, Soria-Juan B, et al. Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide. Antioxidants. 2021 Sep 2;10(9):1408