Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival
| Autor: | Rafael Tapia-Limonchi, Juan R. Tejedo, Franz Martín, S Mora-Castilla, Francisco J. Bedoya, Bernat Soria, Gladys M. Cahuana, Abdelkrim Hmadcha |
|---|---|
| Přispěvatelé: | Centro Andaluz de Investigaciones en Biología Molecular y Medina Regenerativa (CABIMER), Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), [Tejedo,JR, Mora-Castilla,S, Cahuana,GM, Martin,F, Bedoya,FJ] Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER)-University Pablo de Olavide, CIBERDEM, Seville, Spain. [Tapia-Limonchi,R, Hmadcha,A, Soria,B] Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER)-Fundación Progreso y Salud, Seville, Spain, This study was supported by grants from Dirección General de Investigación Científica y Técnica (SAF2007/60105) and Junta de Andalucía (CTS576) to FJB, from Instituto de Salud Carlos III (TERCEL RD06/0010/0025), Fondo de Investigaciones Sanitarias (FIS-052106) and Dirección General de Investigación Científica y Técnica (CYT-836, SAF2005-08014) to BS, from Dirección General de Investigación Científica y Técnica (SAF2006-06673), Junta de Andalucíaa (exp. 0009/06, PI0022) and Instituto de Salud Carlos III (RETIC RD06/ 0015/0013 and CIBERDEM) to FM, from Consejería de Salud-Fundación Progreso y Salud (S0051) to A. Hmadcha, and from Consejería de Salud-Junta de Andalucia (PI-0095/2007) and Instituto de Salud Carlos III (CIBERDEM) to JRT |
| Rok vydání: | 2011 |
| Předmět: |
Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation [Medical Subject Headings]
Cancer Research Cellular differentiation Cell Apoptosis self-renewal Leukemia Inhibitory Factor Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Mice Chemicals and Drugs::Organic Chemicals::Amines::Polyamines [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] Polyamines Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Transcription Factors::SOX Transcription Factors::SOXB1 Transcription Factors [Medical Subject Headings] Diferenciación celular reproductive and urinary physiology Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::DNA-Binding Proteins::Homeodomain Proteins [Medical Subject Headings] Chemicals and Drugs::Biological Factors::Biological Markers::Antigens Differentiation::Antigens CD::Antigens CD15 [Medical Subject Headings] Cell Differentiation differentiation Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Transcription Factors::POU Domain Factors::Octamer Transcription Factors::Octamer Transcription Factor-3 [Medical Subject Headings] medicine.anatomical_structure Factor Inhibidor de Leucemia Differentiation embryonic structures Self-renewal Original Article Homeobox protein NANOG Nitric Oxide Synthase Type III Células madre embrionarias Cell Survival Immunology Lewis X Antigen Caspase 3 Biology Nitric Oxide Cellular and Molecular Neuroscience Downregulation and upregulation SOX2 Anatomy::Cells::Stem Cells::Embryonic Stem Cells [Medical Subject Headings] Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Survival [Medical Subject Headings] medicine Animals Humans Embryonic Stem Cells Homeodomain Proteins Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Óxido Nítrico SOXB1 Transcription Factors Cell Biology Embryonic stem cell Molecular biology embryonic stem cell Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] Chemicals and Drugs::Inorganic Chemicals::Nitrogen Compounds::Nitrogen Oxides::Nitric Oxide [Medical Subject Headings] Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide Synthase::Nitric Oxide Synthase Type III [Medical Subject Headings] Leukemia inhibitory factor Octamer Transcription Factor-3 |
| Zdroj: | Cell Death & Disease idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| ISSN: | 2041-4889 |
| Popis: | Journal Article; Research Support, Non-U.S. Gov't; Nitric oxide (NO) is an intracellular messenger in several cell systems, but its contribution to embryonic stem cell (ESC) biology has not been characterized. Exposure of ESCs to low concentrations (2-20 μM) of the NO donor diethylenetriamine NO adduct confers protection from apoptosis elicited by leukaemia inhibitory factor (LIF) withdrawal. NO blocked caspase 3 activation, PARP degradation, downregulation of the pro-apoptotic genes Casp7, Casp9, Bax and Bak1 and upregulation of the anti-apoptotic genes Bcl-2 111, Bcl-2 and Birc6. These effects were also observed in cells overexpressing eNOS. Exposure of LIF-deprived mESCs to low NO prevented the loss of expression of self-renewal genes (Oct4, Nanog and Sox2) and the SSEA marker. Moreover, NO blocked the differentiation process promoted by the absence of LIF and bFGF in mouse and human ESCs. NO treatment decreased the expression of differentiation markers, such as Brachyury, Gata6 and Gata4. Constitutive overexpression of eNOS in cells exposed to LIF deprivation maintained the expression of self-renewal markers, whereas the differentiation genes were repressed. These effects were reversed by addition of the NOS inhibitor L-NMMA. Altogether, the data suggest that low NO has a role in the regulation of ESC differentiation by delaying the entry into differentiation, arresting the loss of self-renewal markers and promoting cell survival by inhibiting apoptosis. Yes |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|