Abstract 9546: Effects of Endogenous Hydrogen Sulfide on Differentiation of Cardiac Stem Cells
Although hydrogen sulfide (H2S) has recently emerged as a novel gaseous transmitter with important cardioprotective properties, nothing is known regarding the role of endogenous H2S in modulating cardiac stem cells (CSCs). To clarify this issue, murine lin(-)c-kit(+) CSCs were pretreated with NaHS (an H2S donor) at a physiological concentration of 100 uM or β-cyano-L-alanine (BCA, 2 mM) and DL-propargylglycine (PAG, 2 mM; two inhibitors of H2S biosynthesis), for 24 h in culture media (CM) for flow cytometric analysis, or continually exposed to the same for 72 h in differentiation media (DM) for determining cardiac protein expression. After 72 h of differentiation, the levels of three major markers, von Willebrand factor (VWF) for endothelial cell (EC), α-smooth muscle actin (α-SMA) for smooth muscle cell (SMC), and α-sarcomeric actin (α-Src) for myocytes, did not change in NaHS treated-differentiated CSCs but were significantly increased in BCA or PAG treated-differentiated CSCs as compared with the differentiated control CSCs (n=4, P<0.05, Fig. A). Furthermore, at 24 h of treatment in the culture media, flow cytometric analysis revealed that NaHS treatment did not change the transcription factors expressed early in the cardiac lineages (Ets-1 for EC; GATA-6 for SMC; GATA-4, MEF-2C and Nkx-2.5 for myocytes), whereas BCA or PAG resulted in markedly elevated expression of Ets-1, MEF-2C, and Nkx-2.5 in CSCs (n=5, P<0.05, Fig. B). These data demonstrate, for the first time, that endogenous H2S is involved in the lineage specification of adult cardiac stem cells and that it negatively modulates cardiac transcription factors Ets-1, MEF-2C, and Nkx-2.5, thereby providing insights into myogenesis.
- Stem cells
- Biology, developmental
- Signal transduction
- Cardiac regeneration
- Regenerative medicine stem cells
- © 2011 by American Heart Association, Inc.