scholarly journals Apolipoprotein E Enhances Endothelial-NO Production by Modulating Caveolin 1 Interaction With Endothelial NO Synthase

Hypertension ◽  
2012 ◽  
Vol 60 (4) ◽  
pp. 1040-1046 ◽  
Author(s):  
Lili Yue ◽  
Jing-Tan Bian ◽  
Ivana Grizelj ◽  
Ana Cavka ◽  
Shane A. Phillips ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
No Synthase ◽  
No Production ◽  
Caveolin 1 ◽  
Endothelial No Synthase

scholarly journals Commutative regulation between endothelial NO synthase and insulin receptor substrate 2 by microRNAs

2018 ◽  
Vol 11 (6) ◽  
pp. 510-521 ◽  
Author(s):  
Xiaoli Sun ◽  
Huizhen Lv ◽  
Peng Zhao ◽  
Jinlong He ◽  
Qinghua Cui ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Insulin Receptor ◽  
No Synthase ◽  
Luciferase Reporter ◽  
Common Disease ◽  
Enos Gene ◽  
No Production ◽  
Insulin Receptor Substrate ◽  
Endothelial No Synthase ◽  
Mrna Targets

Abstract Endothelial NO synthase (eNOS) expression is regulated by a number of transcriptional and post-transcriptional mechanisms, but the effects of competing endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still unknown. Our bioinformatic analysis revealed three highly expressed eNOS-targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs). Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common disease association with eNOS. Gene expression and correlation analysis in patients with cardiovascular diseases identified insulin receptor substrate 2 (IRS2) as the most correlated eNOS-ceRNA. The expression levels of eNOS and IRS2 were coincidentally increased by application of laminar shear but reduced with eNOS or IRS2 siRNA transfection in human ECs, which was impeded by Dicer siRNA treatment. Moreover, luciferase reporter assay showed that these three miRNAs directly target the 3′UTR of eNOS and IRS2. Overexpression of these three miRNAs decreased, whereas inhibition of them increased, both mRNA and protein levels of eNOS and IRS2. Functionally, silencing eNOS suppressed the Akt signal pathway, while IRS2 knockdown reduced NO production in ECs. Thus, we identified eNOS and IRS2 as ceRNAs and revealed a novel mechanism explaining the coincidence of metabolic and cardiovascular diseases.

17β-Estradiol decreases hypoxic induction of erythropoietin gene expression

2002 ◽  
Vol 283 (2) ◽  
pp. R496-R504 ◽  
Author(s):  
Harshini Mukundan ◽  
Thomas C. Resta ◽  
Nancy L. Kanagy
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Oxygen Delivery ◽  
Chronic Hypoxia ◽  
No Synthase ◽  
No Production ◽  
Enos Expression ◽  
Hypoxic Induction ◽  
Endothelial No Synthase ◽  
17Β Estradiol

Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17β-estradiol (E2-β) inhibits this effect. We hypothesized that E2-β decreases EPO gene expression during hypoxia. Because E2-β can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-β inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-β (20 μg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O2) or normoxia. We found that E2-β treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-β treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-β decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.

Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

2008 ◽  
Vol 294 (1) ◽  
pp. C295-C305 ◽  
Author(s):  
James White ◽  
Theresa Guerin ◽  
Hollie Swanson ◽  
Steven Post ◽  
Haining Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myristic Acid ◽  
Acetylcholine Receptors ◽  
Diabetic Mouse ◽  
No Synthase ◽  
Diabetic Patients ◽  
No Production ◽  
Dependent Manner ◽  
Endothelial No Synthase ◽  
Stimulation Of

In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

scholarly journals Cell Cycle-Regulated Inactivation of Endothelial NO Synthase through NOSIP-Dependent Targeting to the Cytoskeleton

2005 ◽  
Vol 25 (18) ◽  
pp. 8251-8258 ◽  
Author(s):  
Michael Schleicher ◽  
Fredrik Brundin ◽  
Steffen Gross ◽  
Werner Müller-Esterl ◽  
Stefanie Oess
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Vascular Function ◽  
No Synthase ◽  
Nuclear Localization Sequence ◽  
No Production ◽  
Endothelial No Synthase ◽  
Importin Α

ABSTRACT Nitric oxide (NO) plays a key role in vascular function, cell proliferation, and apoptosis. Proper subcellular localization of endothelial NO synthase (eNOS) is crucial for its activity; however, the role of eNOS trafficking for NO biosynthesis remains to be defined. Overexpression of NOS-interacting protein (NOSIP) induces translocation of eNOS from the plasma membrane to intracellular compartments, thereby impairing NO production. Here we report that endogenous NOSIP reduces the enzymatic capacity of eNOS, specifically in the G2 phase of the cell cycle by targeting eNOS to the actin cytoskeleton. This regulation is critically dependent on the nucleocytoplasmic shuttling of NOSIP and its cytoplasmic accumulation in the G2 phase. The predominant nuclear localization of NOSIP depends on a bipartite nuclear localization sequence (NLS) mediating interaction with importin α. Mutational destruction of the NLS abolishes nuclear import and interaction with importin α. Nuclear export is insensitive to leptomycin B and hence different from the CRM1-dependent default mechanism. Inhibition of NOSIP expression by RNA interference completely abolishes G2-specific cytoskeletal association and inhibition of eNOS. These findings describe a novel cell cycle-dependent modulation of endogenous NO levels that are critical to the cell cycle-related actions of NO such as apoptosis or cell proliferation.

scholarly journals Role of Gi/o-Src kinase-PI3K/Akt pathway and caveolin-1 in β2-adrenoceptor coupling to endothelial NO synthase in mouse pulmonary artery

2011 ◽  
Vol 23 (7) ◽  
pp. 1136-1143 ◽  
Author(s):  
Sébastien Banquet ◽  
Estelle Delannoy ◽  
Abdelali Agouni ◽  
Chantal Dessy ◽  
Sabrina Lacomme ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Src Kinase ◽  
No Synthase ◽  
Akt Pathway ◽  
Caveolin 1 ◽  
Endothelial No Synthase

Effect of renal injury-induced neurogenic hypertension on NO synthase, caveolin-1, AKt, calmodulin and soluble guanylate cyclase expressions in the kidney

2007 ◽  
Vol 292 (3) ◽  
pp. F974-F980 ◽  
Author(s):  
Y. Bai ◽  
S. Ye ◽  
R. Mortazavi ◽  
V. Campese ◽  
N. D. Vaziri
Keyword(s):  
Arterial Pressure ◽  
Guanylate Cyclase ◽  
Renal Injury ◽  
Soluble Guanylate Cyclase ◽  
Left Kidney ◽  
Renal Tissue ◽  
No Synthase ◽  
No Production ◽  
Caveolin 1 ◽  
Nos Isoforms

Single injection of a small quantity of phenol into the cortex of one kidney in rats results in development of persistent hypertension (HTN) which is thought to be mediated by activation of renal afferent and efferent sympathetic pathways and sodium retention. Nitric oxide (NO) plays a major role in regulation of renal vascular resistance, tubular Na+ reabsorption, pressure natriuresis, and thereby systemic arterial pressure. The present study was performed to test the hypothesis that chronic renal injury-induced HTN may be associated with dysregulation of NO system in the kidney. Accordingly, urinary NO metabolite (NOx) and cGMP excretions as well as renal cortical tissue (right kidney) expressions of NO synthase (NOS) isoforms [endothelial, neuronal, and inducible NOS, respectively (eNOS, nNOS, and iNOS)], NOS-regulatory factors (Caveolin-1, phospho-AKt, and calmodulin), and second-messenger system (soluble guanylate cyclase [sGC] and phosphodiesterase-5 [PDE-5]) were determined in male Sprague-Dawley rats 4 wk after injection of phenol (50 μl of 10% phenol) or saline into the lower pole of left kidney. The phenol-injected group exhibited a significant elevation of arterial pressure, marked reductions of urinary NOx and cGMP excretions, downregulations of renal tissue nNOS, eNOS, Phospho-eNOS, iNOS, and alpha chain of sGC. However, renal tissue AKt, phospho-AKT, Calmodulin, and PDE-5 proteins were unchanged in the phenol-injected animals. In conclusion, renal injury in this model results in significant downregulations of NOS isoforms and sGC and consequent reductions of NO production and cGMP generation by the kidney, events that may contribute to maintenance of HTN in this model.

scholarly journals Protein kinase B/Akt activates c-Jun NH2-terminal kinase by increasing NO production in response to shear stress

2001 ◽  
Vol 91 (4) ◽  
pp. 1574-1581 ◽  
Author(s):  
Young-Mi Go ◽  
Yong Chool Boo ◽  
Heonyong Park ◽  
Matthew C. Maland ◽  
Rakesh Patel ◽  
...  
Keyword(s):  
Shear Stress ◽  
Protein Kinase ◽  
Transient Expression ◽  
Protein Kinase B ◽  
No Synthase ◽  
No Production ◽  
Endothelial No Synthase ◽  
Jnk Activation ◽  
Adenoviral Construct ◽  
Stimulation Of

Laminar shear stress activates c-Jun NH2-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (AktAA) and a constitutively active mutant (AktMyr) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of AktAA in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of AktMyr by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O[Formula: see text], which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

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