High nitric oxide production, secondary to inducible nitric oxide synthase expression, is essential for regulation of the tumour-initiating properties of colon cancer stem cells

2015 ◽  
Vol 236 (4) ◽  
pp. 479-490 ◽  
Author(s):  
Maria Ausiliatrice Puglisi ◽  
Carlo Cenciarelli ◽  
Valentina Tesori ◽  
Marianna Cappellari ◽  
Maurizio Martini ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Colon Cancer ◽  
Nitric Oxide Synthase ◽  
Cancer Stem Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Production ◽  
Colon Cancer Stem Cells ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase.

1995 ◽  
Vol 181 (1) ◽  
pp. 63-70 ◽  
Author(s):  
N K Worrall ◽  
W D Lazenby ◽  
T P Misko ◽  
T S Lin ◽  
C P Rodi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Biologically Active ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The role of nitric oxide in the immune response to allogeneic tissue was explored in an in vivo cardiac transplant model in the rat. Nitric oxide production during organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the inducible nitric oxide synthase enzyme was detected in the rejecting allografted heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated to be biologically active by the in vitro conversion of L-arginine to L-citrulline and was immunohistochemically localized to the infiltrating inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, prevented the increased nitric oxide production in the transplanted organ and significantly attenuated the pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection. These results suggest an important role for nitric oxide in mediating the immune response to allogeneic tissue. Inhibition of inducible nitric oxide synthase may provide a novel therapeutic modality in the management of acute transplant rejection and of other immune-mediated processes.

scholarly journals Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells

2018 ◽  
Vol 51 (2) ◽  
pp. 746-762 ◽  
Author(s):  
Jin-Sun Lee ◽  
Hong Jae Lee ◽  
Jae Won Lee ◽  
Sang Cheon  Lee ◽  
Jung Sun Heo
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nitric Oxide Synthase ◽  
Cell Viability ◽  
Osteogenic Differentiation ◽  
Inducible Nitric Oxide Synthase ◽  
Embryonic Stem ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background/Aims: This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). Methods: We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO3) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3’,5’ monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. Results: Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. Conclusion: These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.

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