Characterization of Monoamine Oxidases in Mesenchymal Stem Cells: Role in Hydrogen Peroxide Generation and Serotonin-Dependent Apoptosis
| العنوان: | Characterization of Monoamine Oxidases in Mesenchymal Stem Cells: Role in Hydrogen Peroxide Generation and Serotonin-Dependent Apoptosis |
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| المؤلفون: | Angelo Parini, Céline Mias, Catherine Ordener, Marie-Hélène Seguelas, Elodie Trouche, Daniel Cussac |
| المساهمون: | Simon, Marie Francoise, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées |
| المصدر: | Stem Cells and Development Stem Cells and Development, 2010, 19 (10), pp.1571-8. ⟨10.1089/scd.2009.0353⟩ Stem Cells and Development; Vol 19 |
| بيانات النشر: | Mary Ann Liebert Inc, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Imipramine, Cell, Apoptosis, 030204 cardiovascular system & hematology, 0302 clinical medicine, MESH: Oxidants, MESH: Animals, Sympathomimetics, MESH: Serotonin Plasma Membrane Transport Proteins, Cells, Cultured, MESH: Adrenergic Uptake Inhibitors, Serotonin transporter, bcl-2-Associated X Protein, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, Adrenergic Uptake Inhibitors, biology, MESH: Imipramine, Cytochromes c, MESH: Cytochromes c, Hematology, Oxidants, Cell biology, Isoenzymes, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Biochemistry, MESH: Isoenzymes, MESH: Hydrogen Peroxide, MESH: Rats, Inbred Lew, Monoamine oxidase A, MESH: Tyramine, MESH: Cells, Cultured, medicine.drug, Serotonin, Monoamine Oxidase Inhibitors, MESH: Rats, MESH: Monoamine Oxidase Inhibitors, Tyramine, MESH: Pargyline, MESH: Monoamine Oxidase, 03 medical and health sciences, medicine, Animals, MESH: bcl-2-Associated X Protein, Monoamine Oxidase, 030304 developmental biology, MESH: Apoptosis, MESH: Sympathomimetics, Mesenchymal stem cell, Mesenchymal Stem Cells, Hydrogen Peroxide, Cell Biology, Pargyline, Rats, MESH: Mesenchymal Stem Cells, Monoamine neurotransmitter, MESH: Proto-Oncogene Proteins c-bcl-2, Rats, Inbred Lew, biology.protein, MESH: Serotonin, Developmental Biology |
| الوصف: | International audience; Early death of grafted bone marrow mesenchymal stem cells (MSCs) represents a major limit to their use in cell therapy of solid organs. It is well known that oxidative stress plays a major role in cell death. We have recently shown that the serotonin-degrading enzyme monoamine oxidase A (MAO-A) generates large amount of hydrogen peroxide (H2O2) responsible for cell apoptosis. Hydrogen peroxide generation requires 5-HT internalization into the cell and its degradation by MAO-A. In the present study, we investigated whether MAO-A is expressed in MSCs and we defined its role in serotonin-dependent MSCs apoptosis. RT-PCR analysis and western blots showed that the serotonin transporter (SERT) and the 2 MAO isoenzymes, A and B, are expressed in MSCs. As shown by enzyme assays using [14C]serotonin or [14C]β-phenylethylamine as selective MAO-A or MAO-B substrates, MAO-A is largely predominant in MSCs. Incubation of MSCs with the MAO substrate tyramine led to a time-dependent generation of H2O2 that was prevented by the MAO inhibitor pargyline. Finally, exposure of the cells to serotonin promoted an increase in MSCs apoptosis prevented by pargyline and the SERT inhibitor imipramine. The pro-apoptotic effect of serotonin was associated to a decrease in the expression of the anti-apoptotic factor Bcl-2. In conclusion, these results show for the first time that the 5-HT-degrading enzyme MAO-A is an important source of H2O2 in MSCs and plays a major role in 5-HT-dependent MSCs apoptosis. |
| تدمد: | 1557-8534 1547-3287 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbf108ce444fe12f97013e87f83a116e https://doi.org/10.1089/scd.2009.0353 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cbf108ce444fe12f97013e87f83a116e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15578534 15473287 |
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