Reactive oxygen species and upregulation of NADPH oxidases in mechanotransduction of embryonic stem cells.
Deciphering the differentiation pathway of embryonic stem (ES) cells is a challenging task not only for basic research, but also for clinicians who intend to use ES cells for cell transplantation approaches. We have shown that reactive oxygen species (ROS) play a primordial role in the differentiation of mouse ES cells toward the cardiovascular cell lineage. During differentiation, ES cells robustly generate ROS, which interfere with signaling pathways that direct cardiac and vascular commitment. Differentiating ES cells expression of Nox-1, Nox-2, and Nox-4 has been demonstrated. We have shown that mechanical strain application to embyoid bodies grown from ES cells initiates the cardiovascular differentiation program. Under these conditions, a burst of ROS generation occurs which is followed by induction of Nox-1 and Nox-4 and a feed-forward upregulation of ROS production.
Sauer
Heinrich
H
Department of Physiology, Justus Liebig University, Giessen, Germany.
Ruhe
Carola
C
Müller
Jörg P
JP
Schmelter
Maike
M
D'Souza
Rochelle
R
Wartenberg
Maria
M
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D020868:Gene Silencing; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics*
D007527:Isoenzymes; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases