Oxygen Reduction by Nitric-oxide Synthases

Stuehr, Dennis J.; Pou, Sovitj; Rosen, Gerald M.

doi:10.1074/jbc.r100011200

Cited by 373 publications

(261 citation statements)

References 77 publications

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“…Endothelin through ET-B receptor augments ox-LDL uptake in plaques and upregulates lectin-like ox-LDL receptor-1 mRNA that facilitates ox-LDL internalization [78,79]. A process called Buncoupling^of eNOS is initiated triggering the production of superoxide anions (O 2 − ) [80,81]. This potent free radical is a messenger molecule and, in a vicious cycle, propels the production of ox-LDL.…”

Section: Endothelial Dysfunction-a Hallmark Of Cardiovascular Diseasementioning

confidence: 99%

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

et al. 2017

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The endothelium has increasingly been recognized as a smart barrier and a key regulator of blood flow in microand macrovascular beds. Endothelial dysfunction marks a stage of atherosclerosis and is an important prognostic marker for cardiovascular disease. Yet, some people who tend to be slim and physically active and with rather low blood pressure show a propensity to respond to certain stimuli such as emotional stress with endothelial-mediated vascular dysregulation (Flammer syndrome). This leads to characteristic vascular symptoms such as cold hands but also a risk for vascularmediated diseases such as normal-tension glaucoma. It is the aim of this review to delineate the differences between Flammer syndrome and its Bcounterpart^endothelial dysfunction in the context of cardiovascular diseases.

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Section: Endothelial Dysfunction-a Hallmark Of Cardiovascular Diseasementioning

confidence: 99%

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

et al. 2017

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“…In humans, there exist three different isoforms of NOS known as: neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3) [17]. All isoforms of NOS utilize L-arginine as a substrate along with oxygen and reduced nicotinamide-adenine-dinucleotide phosphate as co-substrates [18]. In addition, all isoforms of NOS bind calmodulin and calcium; activated calmodulin is important for the regulation of eNOS and nNOS activity [19].…”

Section: Physiology Of Vascular Tonementioning

confidence: 99%

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

2013

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Methylene blue is used primarily in the treatment of patients with methemoglobinemia. Most recently, methylene blue has been used as a treatment for refractory distributive shock from a variety of causes such as sepsis and anaphylaxis. Many studies suggest that the nitric oxidecyclic guanosine monophosphate (NO-cGMP) pathway plays a significant role in the pathophysiology of distributive shock. There are some experimental and clinical experiences with the use of methylene blue as a selective inhibitor of the NO-cGMP pathway. Methylene blue may play a role in the treatment of distributive shock when standard treatment fails.

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“…Simultaneously, the increased SO production inhibits eNOS NO biosynthesis [3,4] and degrades NO [5], thus further contributing to diabetic endothelial dysfunction. Under these conditions, eNOS 'uncoupling' results in SO formation over NO production [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…BH4 is finally produced through further steps catalysed by 6-pyruvol-tetrahydropterin synthase and sepiapterin reductase [10]. BH4 appears to facilitate electron transfer from the reductase domain to the oxygenase domain of NOS, and maintains the haem prosthetic group in its redox active form [6,7,11]. Furthermore, BH4 also promotes and possibly stabilises eNOS protein in the active homodimer formation [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation

et al. 2005

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Aims/hypothesis: Impaired nitric oxide (NO) bioactivity and increased superoxide (SO) production are characteristics of vascular endothelial dysfunction in diabetes. The underlying mechanisms remain unknown. In this regard, we investigated the role of tetrahydrobiopterin (BH4) bioavailability in regulating endothelial nitric oxide synthase (eNOS) activity, dimerisation and SO production in streptozotocin-induced diabetic mice. Methods: Mouse aortas were used for assays of the following: (1) aortic function by isometric tension; (2) NO by electronic paramagnetic resonance; (3) SO by lucigenin-enhanced chemiluminescence and dihydroethidine fluorescence; (4) total biopterin and BH4 by high-performance liquid chromatography; and (5) eNOS protein expression and dimerisation by immunoblotting. Results: In diabetic mouse aortas, relaxations to acetylcholine and NO levels were significantly decreased, but SO production was increased, in association with reductions in total biopterins and BH4. Although total eNOS levels were increased in diabetes, the protein mainly existed in monomeric form. Conversely, specifically augmented BH4 in diabetic endothelium preserved eNOS dimerisation, but the expression remained unchanged. Conclusions/interpretation: Our results demonstrate that BH4 plays an important role in regulating eNOS activity and its functional protein structure, suggesting that increasing endothelial BH4 and/or protecting it from oxidation may be a rational therapeutic strategy to restore eNOS function in diabetes.

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Oxygen Reduction by Nitric-oxide Synthases

Cited by 373 publications

References 77 publications

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation

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