Furthermore, superoxide anions can modify endothelial function by reducing nitric oxide (NO) biosynthesis and bioavailability [ 7 ]. (hindawi.com)
Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. (ox.ac.uk)
Without this recycling process, uncoupling of the endothelial nitric oxide synthase (eNOS) enzyme and reduced bioavailability of the vasodilator nitric oxide occur, creating a form of endothelial dysfunction. (wikipedia.org)
Resveratrol downregulates the expression and activity of the oxidase inhibiting NADPH oxidase-mediated production of reactive oxygen species (ROS), stimulates mitochondria biogenesis reducing mitochondrial superoxide generation and upregulates the tetrahydrobiopterin-synthesizing enzyme guanosine triphosphate (GTP) cyclohydrolase I preventing superoxide production from uncoupled endothelial nitric oxide synthase. (encyclopedia.pub)
In cases of such stress, it was observed that BH4 itself, sepiapterin, folic acid, resveratrol, and a small-molecular-weight compound AVE3085 have the ability to recouple endothelial nitric oxide synthase (eNOS) and improve endothelial function. (medscape.com)
Role of nitric oxide on purinergic signalling in the cochlea Harada, Narinobu 2010-06-08 00:00:00 In the inner ear, there is considerable evidence that extracellular adenosine 5′-triphosphate (ATP) plays an important role in auditory neurotransmission as a neurotransmitter or a neuromodulator, although the potential role of adenosine signalling in the modulation of auditory neurotransmission has also been reported. (sagepub.com)
GTPCH3
We have now investigated the importance and mechanisms of BH4 availability in vivo using a novel transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, guanosine triphosphate-cyclohydrolase I (GTPCH). (ox.ac.uk)
Sapropterin is indicated in tetrahydrobiopterin deficiency caused by GTP cyclohydrolase I (GTPCH) deficiency, or 6-pyruvoyltetrahydropterin synthase (PTPS) deficiency. (wikipedia.org)
Tetrahydrobiopterin is biosynthesized from guanosine triphosphate (GTP) by three chemical reactions mediated by the enzymes GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR). BH4 can be oxidized by one or two electron reactions, to generate BH4 or BH3 radical and BH2, respectively. (wikipedia.org)
Superoxide2
Endothelial cell superoxide production in diabetes was increased, and NO-mediated endothelium-dependent vasodilatation was impaired. (ox.ac.uk)
In diabetic GCH-Tg mice, superoxide production from the endothelium was markedly reduced compared with that of WT mice, endothelial BH4 levels were maintained despite some oxidative loss of BH4, and NO-mediated vasodilatation was preserved. (ox.ac.uk)
Dysfunction2
Hence, endothelial dysfunction, a predictor of several cardiovascular diseases (CVDs), is caused by imbalance between vasodilating and vasoconstricting agents, including NO, endothelium-derived hyperpolarizing factor, prostacyclin, or vasoconstrictive factors such as thromboxane (TXA 2 ) and endothelin-1 (ET-1) [ 8 ]. (hindawi.com)
A 2018 study shows that endothelial cell deficiency in BH4 leads to enhanced vasoconstriction, impaired vasodilation and endothelial cell dysfunction in mice. (medscape.com)
6,7 The mechanism of volatile anesthetic preconditioning (APC), although not fully understood, is believed to share similarities with IPC by activation of adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels, particularly in the mitochondria. (asahq.org)
Vascular5
This issue is of particular relevance since changes in NO release could play an important role in endothelial function maintenance, in addition to regulating proliferation of smooth muscle cells, leukocyte adhesion, platelet aggregation, angiogenesis, thrombosis, vascular tone, and hemodynamics. (hindawi.com)
Increased production of reactive oxygen species and loss of endothelial NO bioactivity are key features of vascular disease states such as diabetes mellitus. (ox.ac.uk)
These findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelial function in diabetes and other vascular disease states. (ox.ac.uk)
Chuaiphichai et al (2017) demonstrated for the first time that selective deficiency in endothelial cell BH4 biosynthesis, via targeted deletion of gene GCHL , is enough to cause eNOS uncoupling, which leads to impaired vascular function in resistance arteries, even without vascular disease. (medscape.com)
[ 15 ] demonstrated a specific role of the endothelial cell BH4 deficiency and eNOS uncoupling in the development of angiotensin II-induced vascular disease. (medscape.com)
Although dexamethasone reduces BH4 levels in endothelial cells, there was no evidence of eNOS uncoupling. (medscape.com)
Production1
The reduced NO production in endothelial cells treated with dexamethasone was mainly attributable to reduced eNOS expression and decreased eNOS phosphorylation at serine 1177. (medscape.com)
Function2
Transport of NO and ROS by AQPs would be required for cell homeostasis to play a critical role in maintaining endothelial function. (hindawi.com)
It was shown that both endothelial cell and macrophage BH4 play important roles in the regulation of NOS function and cellular redox signalling in atherosclerosis. (medscape.com)
Superoxide production3
6. GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial function. (nih.gov)
Endothelial cell superoxide production in diabetes was increased, and NO-mediated endothelium-dependent vasodilatation was impaired. (ox.ac.uk)
In diabetic GCH-Tg mice, superoxide production from the endothelium was markedly reduced compared with that of WT mice, endothelial BH4 levels were maintained despite some oxidative loss of BH4, and NO-mediated vasodilatation was preserved. (ox.ac.uk)
Gch14
9. Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression. (nih.gov)
Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. (cdc.gov)
A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia. (cdc.gov)
Regulation of ß-adrenergic control of heart rate by GTP-cyclohydrolase 1 (GCH1) and tetrahydrobiopterin. (medscape.com)
ENOS6
7. eNOS uncoupling and endothelial dysfunction in aged vessels. (nih.gov)
13. Quantitative regulation of intracellular endothelial nitric-oxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoichiometry and biopterin redox status: insights from cells with tet-regulated GTP cyclohydrolase I expression. (nih.gov)
14. Simvastatin ameliorates angiotensin II-induced endothelial dysfunction through restoration of Rho-BH4-eNOS-NO pathway. (nih.gov)
Without this recycling process, uncoupling of the endothelial nitric oxide synthase (eNOS) enzyme and reduced bioavailability of the vasodilator nitric oxide occur, creating a form of endothelial dysfunction. (wikipedia.org)
These findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelial function in diabetes and other vascular disease states. (ox.ac.uk)
Endothelial NOS (eNOS) is a homodimeric protein that generates NO from the conversion of l -arginine to l -citrulline. (nih.gov)
Increased production of reactive oxygen species and loss of endothelial NO bioactivity are key features of vascular disease states such as diabetes mellitus. (ox.ac.uk)
Acute DE exposure appears to uncouple NOS, increasing reactive oxygen species generation and causing endothelial dysfunction, potentially because of depletion of BH 4 limiting its bioavailability. (nih.gov)
Overexpression2
10. Endothelium-specific GTP cyclohydrolase I overexpression attenuates blood pressure progression in salt-sensitive low-renin hypertension. (nih.gov)
Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. (ox.ac.uk)
Synthesis1
16. Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through the induction of GTP-cyclohydrolase I and increases nitric oxide synthase activity in vascular endothelial cells. (nih.gov)
Gene3
17. GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation. (nih.gov)
Polymorphic variation of the guanosine triphosphate cyclohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. (cdc.gov)
Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population. (cdc.gov)
Arteries1
3. A key role for tetrahydrobiopterin-dependent endothelial NOS regulation in resistance arteries: studies in endothelial cell tetrahydrobiopterin-deficient mice. (nih.gov)
Nitric oxide3
18. Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by increasing tetrahydrobiopterin via regulation of GTP-cyclohydrolase 1 and reducing uncoupled endothelial nitric oxide synthase activity. (nih.gov)
5. Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury. (nih.gov)
Regulation1
4. Cell-autonomous role of endothelial GTP cyclohydrolase 1 and tetrahydrobiopterin in blood pressure regulation. (nih.gov)