Differential expression of genes involved in cGMP-dependent nitric oxide signaling in murine embryonic stem (ES) cells and ES cell-derived cardiomyocytes

Krumenacker, Joshua S.; Katsuki, Shoji; Kots, Alexander Y.; Murad, Ferid

doi:10.1016/j.niox.2005.06.010

Cited by 49 publications

(50 citation statements)

References 30 publications

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“…Therefore, based on these previous observations, we hypothesized that the NOcGMP pathway should influence the differentiation of ES cells into cells of various lineages such as myocardial cells, neural precursor cells, and possibly cells of other lineages. Our previous studies clearly indicate the involvement of NO signaling components in the differentiation of both mouse and human ES cells into cardiomyocytes (18,19).…”

Section: Figmentioning

confidence: 58%

“…In addition, although the slow-release NO donor NOC-18 alone did not show stimulation of cGMP levels, when it was combined with BAY 41-2272 there was a 4-fold increase in cGMP accumulation compared with BAY 41-2272 alone, demonstrating the presence of an activatable sGC as has been described (24) in isolated rat cardiomyocytes. BAY 41-2272 by itself shows some increase in cGMP levels, possibly because of increased NOS-2 and NOS-3 levels in differentiated cells (18,19).…”

Section: Figmentioning

confidence: 99%

“…(Magnification: 20ϫ.) detectable sGC (18,19); therefore, the levels of cGMP in undifferentiated cells are probably caused by particulate guanylyl cyclase. In contrast, although differentiated cells exhibited 7-fold lower levels of basal cGMP compared with undifferentiated cells, a 13-fold stimulation in cGMP accumulation was observed with 100 M NOC-22, demonstrating that differentiated cells acquire the ability to be stimulated with NO.…”

Section: Figmentioning

confidence: 99%

“…Compared with NOS-1, NOS-2, and NOS-3 mRNA and protein levels were also induced during ES cell differentiation (18,19), thereby demonstrating the involvement of NO signaling components during differentiation of ES cells into cardiac cells. Previous studies by other investigators (20) have shown increased cardiomyogenesis with NO donors and by delivery of the NOS-2 gene in mouse ES cells.…”

mentioning

confidence: 92%

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Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells

Mujoo

Sharin

Bryan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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cardiomyogenesis ͉ cyclic GMP ͉ soluble guanylyl cyclase ͉ NO donors ͉ sGC activators E mbryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo, and because of their selfrenewal and pluripotency, they are thought to revolutionize the field of regenerative medicine (1-3). Although transplantation of stem cells into animal models of cardiac injury and Parkinson's disease has revealed some beneficial effects, a better understanding of the role of specific signaling pathways involved in proliferation and differentiation of ES cells is necessary to improve their use in clinical medicine (4-6). Components of a number of signaling pathways such as Wnt/␤-catenin (7), phosphotidyle-inosital 3-kinase (8, 9), MAPK (10), and NO (11) have been shown to regulate proliferation and differentiation of stem cells.NO is a diffusible short-lived free radical and a signaling molecule with a number of important physiological functions such as smooth muscle relaxation, neurotransmission, and inhibition of platelet aggregation and host defense mechanisms (12). It also plays a role in the pathology of several inflammatory diseases and other pathological conditions such as cancer, diabetes, and neurodegenerative diseases (13,14). NO plays an important role in the control of heart rate, contractibility, coronary perfusion, and cardiac development (15, 16). It is synthesized by enzymes called nitric oxide synthases such as NOS-1 (neuronal NOS), NOS-2 (inducible NOS), and NOS-3 (endothelial NOS) that catalyze the oxidation of L-arginine into L-citruline with the release of NO. NO can also be measured in biological systems as metabolites of NO and as nitrites and nitrates (17). The NO receptor soluble guanylyl cyclase (sGC) is a heme-containing heterodimer with ␣ and ␤ subunits (12). Binding of NO to the heme prosthetic group of sGC catalyzes the conversion of GTP into the second messenger cGMP that can exert many physiological effects, such as mediating vascular smooth muscle tone and motility, phototransduction, and maintenance of fluid and electrolyte homeostasis by interaction of cGMP with downstream effectors such as a family of cGMP-dependent protein kinases, cGMP-dependent phosphodiesterases, and cyclic nucleotide gated channels (11).Our previous studies with mouse and human ES cells demonstrated a time-dependent increase in mRNA and protein levels of different subunits of sGC (with the exception of ␤2 mRNA in H-9 cells) during both mouse and human ES cell differentiation into cells of cardiac lineage. Compared with NOS-1, NOS-2, and NOS-3 mRNA and protein levels were also induced during ES cell differentiation (18,19), thereby demonstrating the involvement of NO signaling components during differentiation of ES cells into cardiac cells. Previous studies by other investigators (20) have shown increased cardiomyogenesis with NO donors and by delivery of the NOS-2 gene in mouse ES cells.In this study, we demonstrate the role of NO and cGMP in differentiation of human and mouse ES cells by regulating t...

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Section: Figmentioning

confidence: 58%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 92%

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Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells

Mujoo

Sharin

Bryan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Activity of guanylyl cyclase was determined by RIA (22). Activity of purified human recombinant soluble guanylyl cyclase (23) (from E. Martin, University of Texas, Institute of Molecular Medicine, Houston, TX) was measured as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Kots¹,

Choi²,

Estrella-Jimenez

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis

Alexander

Chau

Tuan

2007

Birth Defects Research

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Our results showed that regulation of NO is essential for normal axial development, that sites of altered NO expression correlate to those of altered apoptosis and dysmorphogenesis, and that CO coadministration resulted in a rectification of normal NO expression. Collectively, these results suggest that alteration in endogenous NO/CO signaling is responsible, at least in part, for the observed NO-induced teratogenesis.

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Differential expression of genes involved in cGMP-dependent nitric oxide signaling in murine embryonic stem (ES) cells and ES cell-derived cardiomyocytes

Cited by 49 publications

References 30 publications

Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells

Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis

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