Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase
| Autor: | Sabine Lange, Martina Buggisch, Bernadette Ateghang, Carola Ruhe, Heinrich Sauer, Catrin Strobel, Maria Wartenberg |
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| Rok vydání: | 2007 |
| Předmět: |
Time Factors
medicine.medical_treatment Cell Blotting Western Biology Gene Expression Regulation Enzymologic chemistry.chemical_compound Mice Catecholamines medicine Myocyte Animals Vitamin E Myocytes Cardiac RNA Messenger Imidazolines Cells Cultured Embryonic Stem Cells Cell Proliferation chemistry.chemical_classification Reactive oxygen species NADPH oxidase Cell growth Reverse Transcriptase Polymerase Chain Reaction Growth factor Acetophenones NADPH Oxidases Cell Differentiation Cell Biology Hydrogen Peroxide Flow Cytometry Molecular biology Embryonic stem cell Immunohistochemistry Actins GATA4 Transcription Factor Isoenzymes medicine.anatomical_structure chemistry Animals Newborn Apocynin cardiovascular system biology.protein Oxidation-Reduction |
| Zdroj: | Journal of cell science. 120(Pt 5) |
| ISSN: | 0021-9533 |
| Popis: | After birth the proliferation of cardiac cells declines, and further growth of the heart occurs by hypertrophic cell growth. In the present study the cell proliferation capacity of mouse embryonic stem (ES) cells versus neonatal cardiomyocytes and the effects of reactive oxygen species (ROS) on cardiomyogenesis and cardiac cell proliferation of ES cells was investigated. Low levels of hydrogen peroxide stimulated cardiomyogenesis of ES cells and induced proliferation of cardiomyocytes derived from ES cells and neonatal mice, as investigated by nuclear translocation of cyclin D1, downregulation of p27Kip1, phosphorylation of retinoblastoma (Rb), increase of Ki-67 expression and incorporation of BrdU. The observed effects were blunted by the free radical scavengers vitamin E and 2-mercaptoglycin (NMPG). In ES cells ROS induced expression of the cardiac-specific genes encoding α-actin, β-MHC, MLC2a, MLC2v and ANP as well as the transcription factors GATA-4, Nkx-2.5, MEF2C, DTEF-1 and the growth factor BMP-10. During differentiation ES cells expressed the NADPH oxidase isoforms Nox-1, Nox-2 and Nox-4. Treatment of cardiac cells with ROS increased Nox-1, Nox-4, p22-phox, p47-phox and p67-phox proteins as well as Nox-1 and Nox-4 mRNA, indicating feed-forward regulation of ROS generation. Inhibition of NADPH oxidase with diphenylen iodonium chloride (DPI) and apocynin abolished ROS-induced cardiomyogenesis of ES cells. Our data suggest that proliferation of neonatal and ES-cell-derived cardiac cells involves ROS-mediated signalling cascades and point towards an involvement of NADPH oxidase in cardiovascular differentiation of ES cells. |
| Databáze: | OpenAIRE |
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