Search results for "Sepiapterin"

2019

Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard ( Podarcis muralis ), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [ sepiapterin reductase ( SPR )] and carotenoid [ beta-carotene oxygenase 2 ( BCO2 )] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin bi…

Role of tetrahydrobiopterin in pulmonary vascular remodelling associated with pulmonary fibrosis

2013

[Background]: Pulmonary hypertension in idiopathic pulmonary fibrosis (IPF) is indicative of a poor prognosis. Recent evidence suggests that tetrahydrobiopterin (BH4), the cofactor of nitric oxide synthase (NOS), is involved in pulmonary hypertension and that pulmonary artery endothelial-to-mesenchymal transition (EnMT) may contribute to pulmonary fibrosis. However, the role of BH4 in pulmonary remodelling secondary to pulmonary fibrosis is unknown. This study examined the BH4 system in plasma and pulmonary arteries from patients with IPF as well as the antiremodelling and antifibrotic effects of the BH4 precursor sepiapterin in rat bleomycin-induced pulmonary fibrosis and in vitro EnMT mod…

Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System

2009

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti-atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due to increased NO inactivation by reactive oxygen species and reduced NO synthesis. Various types of vascular pathophysiology are associated with oxidative stress, with NADPH oxidases as the major source of reactive oxygen species. These inactivate NO. Also, oxidative stress is likely to be the main cause for oxidation of the essential NOS cofactor, tetrahydrobiopterin (BH(4)). A lack of BH(4) leads to eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO synthesis in eNOS). Based on these pathomechanisms, the therapeutic pot…

Pharmacological prevention of eNOS uncoupling.

2013

Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). This endothelium-derived NO is a protective molecule with antihypertensive, antithrombotic and anti-atherosclerotic properties. Cardiovascular risk factors such as hypertension, hypercholesterolemia, cigarette smoking and diabetes mellitus induce oxidative stress mostly by stimulation of the NADPH oxidase. Overproduction of reactive oxygen species leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide- producing enzyme. Consequently, NO …

Use of reversed-phase C18 Sep-Pak cartridges for the purification and concentration of sepiapterin and other pteridines

1985

Abstract Several pteridines have been tested for their ability to bind to C 18 Sep-Pak. Riboflavin, sepiapterin, deoxysepiapterin, 6-acetyl-7,8-dihydropterin, 6-acetyldihydrohomopterin and 3′-hydroxysepiapterin were strongly retained and all but 6-acetyldihydrohomopterin quantitatively recovered upon elution with 2 ml of methanol. The effect of the concentration and volume of the sample, pH and salt concentration on the retention of sepiapterin have been studied. The procedure was very useful for the purification, desalting, solvent exchange and concentration of pteridines having high affinity for the cartridge. C 18 Sep-Pak has been applied succesfully to sample clean-up prior to high-perf…

Sepiapterin reductase in cultured human cells.

1987

Sepiapterin reductase, an enzyme involved in the synthesis of tetrahydrobiopterin (the natural cofactor for phenylalanine, tyrosine and tryptophan hydroxylases), has been assayed in cultured human amniotic fibroblasts and in cultured mononuclear blood cells. In both cases, the Michaelis constants for sepiapterin and NADPH were essentially equal; 20 microM and 6 microM respectively for stimulated mononuclear blood cells and 22 microM and 5 microM respectively for amniotic fibroblasts. The inhibition by N-acetylserotonin was also similar in both cases. The concentration that produced 50% inhibition in stimulated mononuclear blood cells and in amniotic fibroblasts was 2 microM. The results str…

Biopterin metabolism and eNOS expression during hypoxic pulmonary hypertension in mice.

2013

International audience; Tetrahydrobiopterin (BH$_4$), which fosters the formation of and stabilizes endothelial NO synthase (eNOS) as an active dimer, tightly regulates eNOS coupling / uncoupling. Moreover, studies conducted in genetically-modified models demonstrate that BH$_4$ pulmonary deficiency is a key determinant in the pathogenesis of pulmonary hypertension. The present study thus investigates biopterin metabolism and eNOS expression, as well as the effect of sepiapterin (a precursor of BH$_4$) and eNOS gene deletion, in a mice model of hypoxic pulmonary hypertension. In lungs, chronic hypoxia increased BH$_4$ levels and eNOS expression, without modifying dihydrobiopterin (BH$_2$, t…