scholarly journals Oligodendrocyte RasG12V expressed in its endogenous locus disrupts myelin structure through increased MAPK, nitric oxide, and notch signaling

Glia ◽  
2017 ◽  
Vol 65 (12) ◽  
pp. 1990-2002 ◽  
Author(s):  
Haley E. Titus ◽  
Alejandro López-Juárez ◽  
Sadiq H. Silbak ◽  
Tilat A. Rizvi ◽  
Madeleine Bogard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Notch Signaling ◽  
Myelin Structure ◽  
Endogenous Locus

Abstract 380: Notch4 Uncouples Endothelial Nitric Oxide Synthase Leading to Arteriovenous Malformations

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Lawrence Huang ◽  
Matthew A Nystoriak ◽  
Ji Youn Youn ◽  
Manuel F Navedo ◽  
Hua Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Notch Signaling ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Tone ◽  
Superoxide Production ◽  
Nos Inhibitor ◽  
Av Shunt ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Notch is distinctively expressed in arterial but not venous endothelial cells. Notch signaling regulates arteriovenous (AV) specification, and mutations in Notch signaling lead to AV malformation (AVM) in mice. AVMs are characterized by abnormal AV shunts that displace capillaries. Mechanisms underlying AVM pathogenesis remain poorly understood, hindering therapeutic development. We reported that endothelial expression of constitutively active Notch4 (Notch4*) in mice initiates AVMs de novo through enlargement of microvessels without an increase in endothelial cell number or proliferation. Here, we hypothesized that Notch4* disrupts endothelial nitric oxide synthase (eNOS) signaling and vascular tone, thereby permitting vessel enlargement and AV shunting. We show that arteries isolated from Notch4* mutant mice exhibited decreased arterial tone compared to controls, suggesting that Notch4* impaired vascular tone. Administering the NOS inhibitor N G -nitro-L-arginine abolished Notch4*-mediated vascular tone impairment. Deletion of the eNOS gene and administration of the NOS inhibitor N G -nitro-L-arginine in the Notch4* mutant mice attenuated Notch4*-induced AVM initiation, measured by decreased AV shunt diameter, delayed AV shunting, reduced hemorrhage, pathological lesions, and improved survival, suggesting that eNOS is essential for Notch4* action. In addition, uncoupled eNOS-derived superoxide production was elevated in the Notch4* mice. Our results show that inhibition of eNOS signaling attenuates Notch4*-mediated AVM formation. Furthermore, Notch4* impairs eNOS activity, leading to superoxide production, which results in arterial dysfunction and AV shunt formation.

scholarly journals Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

2021 ◽  
Vol 12 ◽  
Author(s):  
Junjie Wen ◽  
Chuxi Chen ◽  
Meiqun Luo ◽  
Xiaocong Liu ◽  
Jiading Guo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Helicobacter Pylori ◽  
Notch Signaling ◽  
Neutralizing Antibody ◽  
Gastrointestinal Diseases ◽  
Stomach Mucosa ◽  
Healthy Control ◽  
Bactericidal Activities ◽  
H Pylori ◽  
Oxide Synthase

Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.

scholarly journals Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

2010 ◽  
Vol 6 (2) ◽  
pp. 141-152 ◽  
Author(s):  
Nikki Charles ◽  
Tatsuya Ozawa ◽  
Massimo Squatrito ◽  
Anne-Marie Bleau ◽  
Cameron W. Brennan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Notch Signaling ◽  
Glioma Cells

scholarly journals Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide‐angiopoietin signaling in a mouse model of peripheral ischemia

2019 ◽  
Vol 26 (6) ◽  
Author(s):  
Maria J. C. Machado ◽  
Rachel Boardman ◽  
Federica Riu ◽  
Costanza Emanueli ◽  
Andrew V. Benest ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Notch Signaling ◽  
Peripheral Ischemia

scholarly journals Downregulation by lipopolysaccharide of Notch signaling, via nitric oxide

2008 ◽  
Vol 121 (9) ◽  
pp. 1466-1476 ◽  
Author(s):  
M.-Y. Kim ◽  
J.-H. Park ◽  
J.-S. Mo ◽  
E.-J. Ann ◽  
S.-O. Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Notch Signaling

Localization of endothelial nitric oxide synthase in the normal and failing human atrial myocardium

1996 ◽  
Vol 54 ◽  
pp. 786-787
Author(s):  
Chi-Ming Wei ◽  
Margarita Bracamonte ◽  
Shi-Wen Jiang ◽  
Richard C. Daly ◽  
Christopher G.A. McGregor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Cardiac Tissues ◽  
Mammalian Tissues ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).

Nitric Oxide Reduces Pressor Responsiveness During Ovine Hypoadrenocorticism

2001 ◽  
Vol 28 (5-6) ◽  
pp. 459-462
Author(s):  
Pini Orbach ◽  
Charles E Wood ◽  
Maureen Keller-Wood
Keyword(s):  
Nitric Oxide
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