Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.19 (NOS)
 7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gestational diabetes is one of the most prevalent medical complications of pregnancy and causes increased fetal wastage. Investigation of placentas from diabetic mothers indicate chronic disturbances in intervillous, circulation, dilatation of capillaries, and a relatively immature villous structure. Abnormal levels of nitric oxide (NO) may contribute to maternal disorders such as the pathogenesis of diabetic vascular complications. In the normal placenta NO is generated only by endothelial NOS, which apparently serves to regulate vascular tone in the fetoplacental circulation. In contrast, studies have reported the absence of inducible nitric oxide synthase (iNOS) in human placentas under normal conditions. The aim of our study was to investigate whether iNOS is expressed in placentas from patients with gestational diabetes. Reverse transcription-polymerase chain reaction and Western blot analysis demonstrated iNOS mRNA and protein expression in placental tissue only from patients with gestational diabetes. Immunohistochemistry localized iNOS staining to endothelial cells and trophoblasts. We conclude that iNOS can be expressed in human placenta. Its expression might play an important role in placental pathophysiology.
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PMID:Expression of inducible nitric oxide synthase in placenta of women with gestational diabetes. 863 95

Reduced oxygen level (hypoxia) induces endothelial dysfunction and release of the endogenous nucleoside adenosine. Human umbilical vein endothelium (HUVEC) function in an environment with 3% to 5% O2 and exhibit efficient adenosine membrane transport via human equilibrative nucleoside transporters 1 (hENT1). We studied whether adenosine transport and hENT1 expression are altered by hypoxia in HUVEC. Hypoxia (0 to 24 hours, 2% and 1% O2) reduced maximal hENT1-adenosine transport velocity (V(max)) and maximal nitrobenzylthionosine (NBMPR, a high-affinity hENT1 protein ligand) binding, but increased extracellular adenosine concentration. Hypoxia also reduced hENT1 protein and mRNA levels, effects unaltered by N(omega)-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase [NOS] inhibitor) or PD-98059 (inhibitor of mitogen-activated protein kinase kinase 1 and 2 [MEK1/2]). Hypoxia reduced endothelial NOS (eNOS) activity and eNOS phosphorylation at Ser(1177), but increased eNOS protein level. Hypoxia increased (1 to 3 hours), but reduced (24 hours) p42/44(mapk) phosphorylation. Thus, hypoxia-increased extracellular adenosine may result from reduced hENT1-adenosine transport in HUVEC. Hypoxia effect seems not to involve NO, but p42/44(mapk) may be required for the relatively rapid effect (1 to 3 hours) of hypoxia. These results could be important in diseases where the fetus is exposed to intrauterine environments poor in oxygen, such as intrauterine growth restriction, or where adenosine transport is altered, such as gestational diabetes.
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PMID:Equilibrative nucleoside transporter 1 expression is downregulated by hypoxia in human umbilical vein endothelium. 1600 53

Human umbilical vein endothelial cells (HUVEC) from gestational diabetes exhibit reduced adenosine uptake and increased nitric oxide (NO) synthesis. Adenosine transport via human equilibrative nucleoside transporters 1 (hENT1) is reduced by NO by unknown mechanisms in HUVEC. We examined whether gestational diabetes-reduced adenosine transport results from lower hENT1 gene (SLC29A1) expression. HUVEC from gestational diabetes exhibit reduced SLC29A1 promoter activity when transfected with pGL3-hENT1(-2154) compared with pGL3-hENT1(-1114) constructs, an effect blocked by N(G)-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), but unaltered by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor). In cells from gestational diabetes transfected with pGL3-hENT1(-2154), L-NAME increased, but SNAP did not alter promoter activity and hENT1 expression. However, in cells from normal pregnancies L-NAME increased, but SNAP reduced promoter activity and hENT1 expression. Adenovirus-silenced eNOS expression increased hENT1 expression and activity in cells from normal or gestational diabetic pregnancies. Thus, reduced adenosine transport may result from downregulation of SLC29A1 expression by NO in HUVEC from gestational diabetes. These findings explain the accumulation of extracellular adenosine detected in cultures of HUVEC from gestational diabetes. In addition, fetal endothelial dysfunction could be involved in the abnormal fetal development and growth seen in gestational diabetes.
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PMID:Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. 1668 63

GDM (gestational diabetes mellitus) is associated with later adverse cardiovascular risk. The present study examined the relationship between glycaemia during pregnancy and small artery function and structures approx. 2 years postpartum. Women were originally enrolled in the HAPO (Hyperglycaemia and Adverse Pregnancy Outcome) study from which they were classified by their glycaemic distribution during pregnancy as controls (in the lower half of the distribution), UQ (upper quartile; in the UQ of the glycaemic distribution) or having had overt GDM. Subcutaneous arteries from a gluteal fat biopsy taken at follow-up 2 years later were examined using wire myography. Small artery structure, stiffness and vasoconstrictor responses were similar across groups. Maximal endothelium-dependent dilation in response to carbachol was impaired in arteries from both GDM (43.3%, n=8 and P=0.01) and UQ (51.7%, n=13 and P=0.04) women despite generally 'normal' current glycaemia (controls, 72.7% and n=8). Inhibition of NOS (nitric oxide synthase) significantly reduced maximum endothelium-dependent dilation in controls but had no effect on arteries from UQ and GDM women, suggesting impaired NOS activity in these groups. Endothelium-independent dilation was unaffected in arteries from previous GDM and UQ women when compared with the control group. Multiple regression analysis suggested that BMI (body mass index) at biopsy was the most potent factor independently associated with small artery function, with no effect of current glycaemia. Overweight women with either GDM or marginally raised glycaemia during pregnancy (our UQ group) had normal vascular structure and stiffness, but clearly detectable progressively impaired endothelium-dependent function at 2 years follow-up. These results suggest that vascular pathology, which may still be reversible, is detectable very early in women at risk of decline into Type 2 diabetes mellitus.
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PMID:Small artery function 2 years postpartum in women with altered glycaemic distributions in their preceding pregnancy. 2174 85

Maternal diabetes-induced neural tube defects (NTDs) are associated with increased programmed cell death (apoptosis) in the neuroepithelium, which is related to intracellular nitrosative stress. To alleviate nitrosative stress, diabetic pregnant mice were fed via gavage an inhibitor of nitric oxide (NO) synthase (NOS) 2, L-N6-(1-iminoethyl)-lysine (L-NIL; 80 mg/kg), once a day from embryonic (E) day 7.5 to 9.5 during early stages of neurulation. The treatment significantly reduced NTD rate in the embryos, compared with that in vehicle (normal saline)-treated diabetic group. In addition to alleviation of nitrosative stress, endoplasmic reticulum (ER) stress was also ameliorated, assessed by quantification of associated factors. Apoptosis was reduced, indicated by caspase 8 activation. These results show that nitrosative stress is important in diabetes-induced NTDs via exacerbating ER stress, leading to increased apoptosis. Oral treatment with NOS-2 inhibitor alleviates nitrosative and ER stress, decreases apoptosis, and reduces NTDs in the embryos, providing information for further interventional studies to reduce diabetes-associated birth defects.
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PMID:Reduction in embryonic malformations and alleviation of endoplasmic reticulum stress by nitric oxide synthase inhibition in diabetic embryopathy. 2253 24

Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e-) vessels. Losartan reduced GDM but not SD e- vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations.
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PMID:Experimental gestational diabetes mellitus induces blunted vasoconstriction and functional changes in the rat aorta. 2561 Aug 61