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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

Authors :
Abdelkrim Hmadcha
Irene Díaz
Gladys M. Cahuana
Bernat Soria
Ana B. Hitos
Franz Martín
Francisco J. Bedoya
Antonio Martínez-Ruiz
Bárbara Soria-Juan
Juan R. Tejedo
Rosario Rodríguez-Griñolo
Estefanía Caballano-Infantes
[Caballano-Infantes,E
Díaz,I
Hitos,AB
Hmadcha,A
Martín,F
Tejedo,JR
Bedoya,FJ] Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain. [Caballano-Infantes,E: Cahuana,GM
Bedoya,FJ] Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain. [Díaz,I
Cahuana,GM
Soria,B
Bedoya,FJ] Biomedical Research Network for Diabetes and Related Metabolic Diseases-CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain. [Martínez-Ruiz,A] Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. [Soria-Juan,B] Fundación Jiménez Díaz Health Research Institute, Madrid, Spain. [Rodríguez-Griñolo,R] Departamento de Economía, Métodos Cuantitativo e Historia Económica, Universidad Pablo de Olavide, Seville, Spain. [Soria,B] ISABIAL and Institute of Bioengineering, University Miguel Hernández de Elche, Alicante, Spain.
E Caballano-Infantes was a doctoral FPU fellow from the Spanish government (FPU12/00184). This study was supported by grants from Consejería de Igualdad, Salud y Políticas Sociales, Junta de Andalucía (PI105/2010, TCMR06/009 and PI-0022) to FJ Bedoya and F Martin
from Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (CTS-7127/2011) to FJ. Bedoya
from ISCIII cofunded by Fondos FEDER (RED-TERCEL RD 16-011-0034) and from Fundación Andaluza de I + D (Grant Al-Andalus Biopharma 2019-2) to B. Soria and from Servicio Andaluz de Salud (SAS 11245) and Ministerio de Economía y Competitividad- Secretaría de Estado de Investigación Desarrollo e Innovación (IPT-2011-1615-900000) to JR Tejedo.
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

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

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