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Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
- Source :
- Antioxidants, Volume 10, Issue 9, Antioxidants, Vol 10, Iss 1408, p 1408 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
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.
- Subjects :
- Physiology
Clinical Biochemistry
Membranas mitocondriales
Biochemistry
Inhibidores de proteasoma
Hydroxylation
Células madre pluripotentes
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
chemistry.chemical_compound
Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::DEET [Medical Subject Headings]
Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Proteasome Endopeptidase Complex [Medical Subject Headings]
Glycolysis
Proteasome inhibitor
Hipoxia
Consumo de oxígeno
Induced pluripotent stem cell
Hypoxia
Mitocondrias
Metabolismo
Phenomena and Processes::Metabolic Phenomena::Metabolome [Medical Subject Headings]
Chemistry
Phenomena and Processes::Metabolic Phenomena::Metabolism::Hydroxylation [Medical Subject Headings]
Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric Oxide [Medical Subject Headings]
Cell biology
Mitochondria
mitochondrial fusion
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::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription Factors [Medical Subject Headings]
medicine.symptom
Homeobox protein NANOG
Pluripotency
Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::Glycolysis [Medical Subject Headings]
normoxia
Oxygen consumption
RM1-950
Anatomy::Cells::Stem Cells::Pluripotent Stem Cells [Medical Subject Headings]
Article
Nitric oxide
Downregulation and upregulation
Pluripotent stem cells
nitric oxide
Phenomena and Processes::Metabolic Phenomena::Oxygen Consumption [Medical Subject Headings]
medicine
Phenomena and Processes::Metabolic Phenomena::Metabolism [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]
Molecular Biology
Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Respiratory::Anoxia [Medical Subject Headings]
Mitochondrial membranes
hypoxia
Hidroxilación
Cell Biology
Hypoxia (medical)
pluripotency
Glucólisis
Metabolism
Therapeutics. Pharmacology
Normoxia
metabolism
Óxido nítrico
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Antioxidants, Volume 10, Issue 9, Antioxidants, Vol 10, Iss 1408, p 1408 (2021)
- Accession number :
- edsair.doi.dedup.....564747978055438567a3bbfbe193457a