ENOS

Am. J. Respir. Cell Mol. Biol. Vol. 23, pp. 762–771, 2000 Internet address: www.atsjournals.org Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including narrowing of the arterial lumen and loss of distal functional arteries. To test whether lung overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) is beneficial in hypoxic PH, recombinant adenovirus encoding the human VEGF 165 gene under the control of a cytomegalovirus promoter (Ad.VEGF) or control vector containing no gene in the expression cassette (Ad.Null) was administered intratracheally to rats. With Ad.VEGF (108 plaque-forming units [pfu]), VEGF protein was present in bronchoalveolar lavage fluid as early as 2 d and until 17 d after gene transfer, but was not detected in serum. Only small patchy areas of

Background— Recent evidence from cultured endothelial cell studies suggests that phosphorylation of endothelial nitric oxide synthase (eNOS) through the PI3-kinase– Akt pathway increases NO production. This study was designed to elucidate the signaling pathway involved in the antiapoptotic effect of insulin in vivo and to test the hypothesis that phosphorylation of eNOS by insulin may participate in the cardioprotective effect of insulin after myocardial ischemia and reperfusion. Methods and Results— Male Sprague-Dawley rats were subjected to 30 minutes of myocardial ischemia and 4 hours of reperfusion. Rats were randomized to receive vehicle, insulin, insulin plus wortmannin, or insulin plus L-NAME. Treatment with insulin resulted in 2.6-fold and 4.3-fold increases in Akt and eNOS phosphorylation and a significant increase in NO production in ischemic/reperfused myocardial tissue. Phosphorylation of Akt and eNOS and increase of NO production by insulin were completely blocked by wo...

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 12.4 years) and 340 age-matched healthy controls (mean age 64.9 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) 3.62, 95% confidence interval (CI): 1.89-7.74, P 0.002), high grade tumor (OR 2.46, 95% CI:1.78-4.72; P 0.006), and advanced disease (OR 4.67, 95% CI: 2.648.61; P 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b "a" variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR 2.12, 95% CI: 1.68-3.44; P 0.031 for 4a/b ab genotype, and OR 4.32, 95% CI: 2.21-6.08; P 0.001 for 4a/b aa genotype). In addition, genotypes with the "a" allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR 4.76, 95% CI: 2.74-8.62; P 0.001) and advanced CaP (OR 5.28, 95% CI: 3.64-8.72; P 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR 0.44, 95% CI: 0.33-0.77; P 0.004, and OR 0.39, 95% CI: 0.26-0.61; P 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.

Wrapped by the Pacific waters and the mist of shipwrecks and pirates stories, one of the rainiest Eastern Pacific islands protects a biodiversity treasure: Isla del Coco. This study presents the analysis of moisture sources linked with contributions to precipitation in the area. The diurnal cycle of precipitation on the island was reviewed from GPS station data previously evaluated using available meteorological data from field campaigns held on the island in 2011 and 2012. Near-surface salinity patterns were also analyzed along with sea surface temperature, evaporation, Ongoing Longwave Radiation (OLR) as well as latent and sensible heat fluxes. Moisture contributions to precipitation on the island are supplied by evaporative sources, and moisture recycling is important. Regional precipitation is a continuous supply of moisture for the atmosphere whereas transport from evaporative sources is seasonally constrained. The analysis of the diurnal cycle of moisture supply suggests that contributions from available moisture linked with precipitation recycling show a slightly delayed response to deep convection in the region. The diurnal cycle of contributions to precipitation from evaporative moisture sources, based on the modeling component of the work, is consistent with the diurnal cycle of precipitation. The trajectory analysis remarks the role of the low level winds, the Intertropical Convergence Zone (ITCZ) position and the stability conditions to modulate the supply of moisture. The moisture contributions from the sources present a different sensitivity to El Niño-Southern Oscillation (ENSO). Contributions from precipitation recycling showed a large variability linked to ENSO as increasing contributions were determined to be related with El Niño during boreal summer and autumn months. The variability of the contributions from a North-east evaporative source is modulated by the response of the Caribbean Low Level Jet (CLLJ; to ENSO. The South-western evaporative source showed sensitivity to El Niño, as transport was found to decrease (increase) from November to March (May to July), meanwhile the response to La Niña was small. Good agreement amongst the ENSO response of the fields and the known dynamics of the region was found. Rev. Biol. Trop. 64 (Suppl. 1): S87-S103. Epub 2016 Febrary 01.

Introduction-Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims-Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods-We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures-Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results-We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signalregulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. Conclusions-These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction.

We aimed to determine whether tocomin, an extract from palm oil that has a high tocotrienol content, was able to prevent diabetes-induced endothelial dysfunction. To induce type 1 diabetes streptozotocin (50 mg/kg) was injected into the tail vein of Wistar rats. Six weeks later the diabetic rats, and normal rats injected with citrate buffer, commenced treatment with tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) for a further 4 weeks. Aortae isolated from diabetic rats had impaired acetylcholine (ACh)-induced endothelium-dependent relaxation compared to normal rat aortae but there was no change in endothelium-independent relaxation in response to sodium nitroprusside. By contrast, responses to ACh in aortae from diabetic rats treated with tocomin were not different to normal rats. In addition to impaired endotheliumdependent relaxation the diabetic aortae had increased expression of the NADPH oxidase Nox2 subunit, increased generation of superoxide and decreased expression of eNOS and all of these effects were prevented by tocomin treatment. Tocomin did not affect plasma glucose levels. The impaired response to ACh in vitro was maintained in the presence of TRAM-34 and apamin, selective inhibitors of calciumactivated potassium (K Ca) channels, indicating diabetes impaired the contribution of NO to endothelium-dependent relaxation. By contrast, neither diabetes nor tocomin treatment influenced EDH-type relaxation as, in the presence of L-NNA, an inhibitor of eNOS, and ODQ, to inhibit soluble guanylate cyclase, responses to ACh were similar in all treatment groups. Thus tocomin treatment improves NO mediated endothelium dependent relaxation in aortae from diabetic rats associated with a decrease in vascular oxidant stress but without affecting hyperglycaemia.

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89-7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78-4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64-8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b "a" variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68-3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21-6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the "a" allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74-8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64-8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33-0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26-0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.

The complex regulation of eNOS (endothelial nitric oxide synthase) in cardiovascular physiology occurs at multiple stages. eNOS mRNA levels are controlled both at the transcriptional and post-transcriptional phases, and epigenetic mechanisms appear to modulate tissue-specific eNOS expression. The eNOS enzyme reversibly associates with a diverse family of protein partners that regulate eNOS sub-cellular localization, catalytic function, and biological activity. eNOS enzyme activity and sub-cellular localization are intimately controlled by posttranslational modifications including phosphorylation, nitrosylation, and acylation. The multiple extra-cellular stimuli affecting eNOS function coordinate their efforts through these key modifications to dynamically control eNOS and NO bioactivity in the vessel wall. This review will focus on the biochemical partners and perturbations of the eNOS protein as this vital enzyme undergoes modulation by diverse signal transduction pathways in the vascular endothelium.