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Cited by 263Nitric Oxide and Endothelin EffectsBiochemical and Molecular ResearchFolate and B Vitamins Research

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP.

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Werner-Felmayer, G., Werner, E.R., Fuchs, D., Hausen, A., Reibnegger, G., Schmidt, K., Weiss, G., Wachter, H.·1993·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)53931-4
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Abstract

Stimulation of nitric oxide (NO) synthase in endothelial cells by Ca2+ influx leads to increased intracellular levels of cGMP. NO synthase from various sources is known to use tetrahydrobiopterin, flavins, and NADPH as cofactors. We studied the effect of interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide on tetrahydrobiopterin biosynthetic activities in human umbilical vein endothelial cells (HUVEC). These stimuli led to an up to 40-fold increase of GTP cyclohydrolase I (EC 3.5.4.16) activity and to increased accumulation of neopterin and tetrahydrobiopterin in HUVEC. Further enzyme activities of tetrahydrobiopterin biosynthesis, i.e. 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153), remained unchanged. NO synthase activity in protein fractions from homogenates of cells treated with interferon-gamma plus tumor necrosis factor-alpha was not influenced as compared with untreated controls. However, interferon-gamma alone or in combination with tumor necrosis factor-alpha significantly increased intracellular cGMP formation in intact HUVEC by 50 and 80%, respectively. These stimuli increased intracellular tetrahydrobiopterin concentrations up to 14-fold. NO-triggered cGMP formation was similarly increased by incubation of otherwise untreated cells with sepiapterin, leading to elevated intracellular tetrahydrobiopterin levels. Thus, cytokines indirectly stimulate the activity of constitutive NO synthase in HUVEC by upregulating production of the cofactor tetrahydrobiopterin.

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Crossref · 10.1016/s0021-9258(18)53931-4

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Research works printed but not linked: 2

  1. Werner-Felmayer, 1990, Cancer Res., 50, 2863
  2. Brown, 1989, Cancer Res., 49, 4941

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Metadata

Authors
Werner-Felmayer, G., Werner, E. R., Fuchs, D., Hausen, A., Reibnegger, G., Schmidt, K., Weiss, G., & Wachter, H.
Affiliations
Universität Innsbruck (AT)
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1993-01
Volume
268
Issue
3
Pages
1842-1846
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/s0021-9258(18)53931-4
OpenAlex
W1496789829
Cited by
263
References
50
Citations by year
2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 6
FWCI
13.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Keywords
pteridine synthesis, tetrahydrobiopterin, nitric oxide synthase, cyclic GMP, endothelial cells, GTP cyclohydrolase I, interferon-gamma, TNF-α, lipopolysaccharide, neopterin, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, sepiapterin
MeSH terms
Amino Acid Oxidoreductases, Biopterins, Cells, Cultured, Endothelium, Vascular, GTP Cyclohydrolase, Cyclic GMP, Humans, Hypoxanthines, Interferon-gamma, Lipopolysaccharides, Nitric Oxide, Pteridines, Pterins, Tumor Necrosis Factor-alpha, Umbilical Veins, Nitric Oxide Synthase, Neopterin

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