Journalartikel
Autorenliste: Bartsch, Caroline; Bekhite, Mohamed M.; Wolheim, Anne; Richter, Madeleine; Ruhe, Carola; Wissuwa, Bianka; Marciniak, Anja; Mueller, Joerg; Heller, Regine; Figulla, Hans-Reiner; Sauer, Heinrich; Wartenberg, Maria
Jahr der Veröffentlichung: 2011
Seiten: 432-443
Zeitschrift: Free Radical Biology and Medicine
Bandnummer: 51
Heftnummer: 2
ISSN: 0891-5849
DOI Link: https://doi.org/10.1016/j.freeradbiomed.2011.04.029
Verlag: Elsevier
Abstract:
Ascorbic acid (AA) increases cardiomyogenesis of embryonic stem (ES) cells. Herein we show that treatment of mouse ES cells with AA enhanced cardiac differentiation accompanied by an upregulation of the NADPH oxidase isoforms NOX2 and NOX4, phosphorylation of endothelial nitric oxide synthase (eNOS), and cyclic GMP (cGMP) formation, indicating that reactive oxygen species (ROS) as well as nitric oxide (NO) may be involved in cardiomyogenesis. In whole mount embryoid bodies as well as isolated Flk-1-positive (Flk-1(+)) cardiovascular progenitor cells ROS elevation by AA was observed in early stages of differentiation (Days 4-7), and absent at Day 10. In contrast NO generation following incubation with AA was absent at Day 4 and increased at Days 7 and 10. AA-mediated cardiomyogenesis was blunted by the NADPH oxidase inhibitors diphenylen iodonium (DPI) and apocynin, the free radical scavengers N-(2-mercaptopropionyl)-glycine (NMPG) and ebselen, and the NOS inhibitor L-NAME. Downregulation of NOX4 by short hairpin RNA (shRNA) resulted in significant inhibition of cardiomyogenesis and abolished the stimulation of MHC-beta and MLC2v gene expression observed on AA treatment. Our data demonstrate that AA stimulates cardiomyocyte differentiation from ES cells by signaling pathways that involve ROS generated at early stages and NO at late stages of cardiomyogenesis. (C) 2011 Elsevier Inc. All rights reserved.
Zitierstile
Harvard-Zitierstil: Bartsch, C., Bekhite, M., Wolheim, A., Richter, M., Ruhe, C., Wissuwa, B., et al. (2011) NADPH oxidase and eNOS control cardiomyogenesis in mouse embryonic stem cells on ascorbic acid treatment, Free Radical Biology and Medicine, 51(2), pp. 432-443. https://doi.org/10.1016/j.freeradbiomed.2011.04.029
APA-Zitierstil: Bartsch, C., Bekhite, M., Wolheim, A., Richter, M., Ruhe, C., Wissuwa, B., Marciniak, A., Mueller, J., Heller, R., Figulla, H., Sauer, H., & Wartenberg, M. (2011). NADPH oxidase and eNOS control cardiomyogenesis in mouse embryonic stem cells on ascorbic acid treatment. Free Radical Biology and Medicine. 51(2), 432-443. https://doi.org/10.1016/j.freeradbiomed.2011.04.029
Schlagwörter
CARDIAC DIFFERENTIATION; Cardiomyocyte differentiation; Cardiomyogenesis; Embryonic stern cells; ES CELLS; MYOCYTES; TETRAHYDROBIOPTERIN; VITAMIN-C
