Journalartikel

Static magnetic fields increase cardiomyocyte differentiation of Flk-1+ cells derived from mouse embryonic stem cells via Ca2+ influx and ROS production


AutorenlisteBekhite, Mohamed M.; Figulla, Hans-Reiner; Sauer, Heinrich; Wartenberg, Maria

Jahr der Veröffentlichung2013

Seiten798-808

ZeitschriftInternational Journal of Cardiology

Bandnummer167

Heftnummer3

ISSN0167-5273

eISSN1874-1754

DOI Linkhttps://doi.org/10.1016/j.ijcard.2012.02.020

VerlagElsevier


Abstract

Aims: To investigate the effects of static magnetic fields (MFs) on cardiomyogenesis of mouse embryonic stem (ES) cell-derived embryoid bodies and Flk-1(+) cardiac progenitor cells and to assess the impact of cytosolic calcium [Ca2+](c) and reactive oxygen species (ROS).

Methods and results: Embryoid bodies and ES cell-derived Flk-1(+) cardiovascular progenitor cells were exposed to static MFs. The expression of cardiac genes was evaluated by RT-PCR; sarcomeric structures were assessed by immunohistochemistry; intracellular ROS and [Ca2+](c) of ES cells were examined by H2DCF-DA- and fluo-4-based microfluorometry. Treatment of embryoid bodies with MFs dose-dependent increased the number of contracting foci and cardiac areas as well as mRNA expression of the cardiac genes MLC2a, MLC2v, alpha-MHC and beta-MHC. In Flk-1(+) cells MFs (1 mT) elevated both [Ca2+](c) and ROS, increased expression of the cardiogenic transcription factors Nkx-2.5 and GATA-4 as well as cardiac genes. This effect was due to Ca2+ influx, since extracellular Ca2+ chelation abrogated ROS production and MF-induced cardiomyogenesis. Furthermore absence of extracellular calcium impaired sarcomere structures. Neither the phospholipase C inhibitor U73122 nor thapsigargin inhibited MF-induced increase in [Ca2+](c) excluding involvement of intracellular calcium stores. ROS were generated through NAD(P) H oxidase, since NOX-4 but not NOX-1 and NOX-2 mRNA was upregulated upon MF exposure. Ablation of NOX-4 by sh-RNA and treatment with the NAD(P) H oxidase inhibitor diphenylen iodonium (DPI) totally abolished MF-induced cardiomyogenesis.

Conclusion: The ability of static MFs to enhance cardiomyocyte differentiation of ES cells allows high throughput generation of cardiomyocytes without pharmacological or genetic modification. (C) 2012 Elsevier Ireland Ltd. All rights reserved.




Zitierstile

Harvard-ZitierstilBekhite, M., Figulla, H., Sauer, H. and Wartenberg, M. (2013) Static magnetic fields increase cardiomyocyte differentiation of Flk-1+ cells derived from mouse embryonic stem cells via Ca2+ influx and ROS production, International Journal of Cardiology, 167(3), pp. 798-808. https://doi.org/10.1016/j.ijcard.2012.02.020

APA-ZitierstilBekhite, M., Figulla, H., Sauer, H., & Wartenberg, M. (2013). Static magnetic fields increase cardiomyocyte differentiation of Flk-1+ cells derived from mouse embryonic stem cells via Ca2+ influx and ROS production. International Journal of Cardiology. 167(3), 798-808. https://doi.org/10.1016/j.ijcard.2012.02.020



Schlagwörter


Cardiomyocytes differentiationCROSS-TALKDOUBLE-BLIND TRIALELECTRICAL-STIMULATIONELECTROMAGNETIC-FIELDSFlk-1(+) cellsINTRACELLULAR CA2+ION-CYCLOTRON-RESONANCEMagnetic fieldsMouse embryonic stem cellsNADPH OXIDASE


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