Cited by 213Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS

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Crabtree, Mark J., Smith, Caroline L., Lam, George, Goligorsky, Michael S., Gross, Steven S.·2008·American Journal of Physiology-Heart and Circulatory Physiology

DOI 10.1152/ajpheart.00823.2007PMC PMC2722919

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Abstract

5,6,7,8-Tetrahydrobiopterin (BH 4 ) is an essential cofactor of nitric oxide synthases (NOSs). Oxidation of BH 4 , in the setting of diabetes and other chronic vasoinflammatory conditions, can cause cofactor insufficiency and uncoupling of endothelial NOS (eNOS), manifest by a switch from nitric oxide (NO) to superoxide production. Here we tested the hypothesis that eNOS uncoupling is not simply a consequence of BH 4 insufficiency, but rather results from a diminished ratio of BH 4 vs. its catalytically incompetent oxidation product, 7,8-dihydrobiopterin (BH 2 ). In support of this hypothesis, [ 3 H]BH 4 binding studies revealed that BH 4 and BH 2 bind eNOS with equal affinity ( K d ≈ 80 nM) and BH 2 can rapidly and efficiently replace BH 4 in preformed eNOS-BH 4 complexes. Whereas the total biopterin pool of murine endothelial cells (ECs) was unaffected by 48-h exposure to diabetic glucose levels (30 mM), BH 2 levels increased from undetectable to 40% of total biopterin. This BH 2 accumulation was associated with diminished calcium ionophore-evoked NO activity and accelerated superoxide production. Since superoxide production was suppressed by NOS inhibitor treatment, eNOS was implicated as a principal superoxide source. Importantly, BH 4 supplementation of ECs (in low and high glucose-containing media) revealed that calcium ionophore-evoked NO bioactivity correlates with intracellular BH 4 :BH 2 and not absolute intracellular levels of BH 4 . Reciprocally, superoxide production was found to negatively correlate with intracellular BH 4 :BH 2 . Hyperglycemia-associated BH 4 oxidation and NO insufficiency was recapitulated in vivo, in the Zucker diabetic fatty rat model of type 2 diabetes. Together, these findings implicate diminished intracellular BH 4 :BH 2 , rather than BH 4 depletion per se, as the molecular trigger for NO insufficiency in diabetes.

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Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine
Griffith, O. W. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90139-6 · Cited by 4,628
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease
Schächinger, V., Britten, M. B., & Zeiher, A. M. (2000) · Circulation · doi:10.1161/01.cir.101.16.1899 · Cited by 2,589
The reaction of NO with superoxide
Huie, R. E., & Padmaja, S. (1993) · Free Radical Research Communications · doi:10.3109/10715769309145868 · Cited by 2,121
Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease
Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T., & Münzel, T. (2001) · Circulation · doi:10.1161/hc4601.099485 · Cited by 1,961
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Landmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Landmesser, U., Dikalov, S., Price, S. R., McCann, L. A., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci14172 · Cited by 1,652
The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide
Pryor, W. A., & Squadrito, G. L. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.268.5.l699 · Cited by 1,511
Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors
Vásquez-Vivar, J., Kalyanaraman, B., Martásek, P., Hogg, N., Masters, B. S. S., Karoui, H., Tordo, P., & Pritchard, K. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9220 · Cited by 1,484

Show all 62 references

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Ćurković, P., Jerbić, B., & Stipanĉić, T. (2010) · InTech eBooks · doi:10.5772/8601 · Cited by 1
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Kern, M., Young, L. H., Rueter, B., Iames, E. S., & Chen, Q. (2011) · Digital Commons - PCOM (Philadelphia College of Osteopathic Medicine) · Cited by 1
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Yakovlev, V. A., & Mikkelsen, R. B. (2014) · Springer eBooks · doi:10.1007/978-3-642-30018-9_118 · Cited by 1
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Mikkelsen, R. B., Yakovlev, V. A., Rabender, C. S., & Alam, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-45594-5_6 · Cited by 1
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González, D. R., Treuer, A. V., & Novoa, U. (2016) · InTech eBooks · doi:10.5772/63668 · Cited by 1
Effects of lacto-vegetarian and vegan diets on glycemic responses and metabolite profiles in healthy adults: A randomized trial using continuous glucose monitoring and targeted metabolomics
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テトラヒドロビオプテリンの細胞膜輸送体活性の測定 : アフリカツメガエル卵母細胞による輸送体遺伝子発現系の応用( ビタミン測定法の現状と課題[IV])
大橋, 晶., 菅原, ゆ., 真々田, 薫., 安西, 尚., 相澤, 信., & 長谷川宏幸 (2011) · ビタミン · doi:10.20632/vso.85.9_485
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Propiedades fotoquímicas de biopterina, neopterina y sus correspondientes dihidroderivados en solución acuosa bajo irradiación UV-A
Vignoni, M. (2011) · doi:10.35537/10915/2763
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Cherng, T. W. (2010) · UNM’s Digital Repository (University of New Mexico)
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Leo, C. H. (2012) · RMIT Research Repository (RMIT University Library) · doi:10.25439/rmt.27340482
The anti-obesogenic effects of nitric oxide.
Sansbury, B. E. (2014) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/1262
The effects of DPP-4 inhibitors on vascular endothelial function in diabetes
Salheen, S. M. (2015) · RMIT Research Repository (RMIT University Library) · doi:10.25439/rmt.27591369
Role of Sepiapterin on endothelial nitric oxide synthase in Acute Kidney Injury: An Enigmatic Story
Juni, R. P., & Moens, A. L. (2011) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31822ba174
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Bertolet, M. L., Minni, M., Galbreath, T., Barsotti, R., Young, L. H., & Chen, Q. (2015) · American Peptide Symposium (APS) · doi:10.17952/24aps.2015.158
Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction
Cerrato, R. (2016) · Figshare
Free Radicals as Atherosclerotic Risk in Relation to Nitric Oxide
Hayashi, T., & Iguchi, A. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-373866-0.00021-6
Arginine, Tetrahydrobiopterin, and Nitric Oxide in Myocardial Protection
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No diabetes mellitus o chá verde melhora o desacoplamento da áxido nítrico sintase renal por restabelecer os valores de tetrahidrobiopterina
Faria, A. M. (2012) · doi:10.47749/t/unicamp.2012.870524

Authors: Crabtree, M. J., Smith, C. L., Lam, G., Goligorsky, M. S., & Gross, S. S.
Affiliations: Cornell University (US)
ORCID: Crabtree, Mark J.
Smith, Caroline L.
Goligorsky, Michael S.
Gross, Steven S.
Venue: American Journal of Physiology-Heart and Circulatory Physiology
Publisher: American Physiological Society
Published: 2008-04
Volume: 294
Issue: 4
Pages: H1530-H1540
ISSN: 0363-6135 (ISSN-L)
1522-1539
DOI: 10.1152/ajpheart.00823.2007
PMC: PMC2722919
OpenAlex: W2148390554
Cited by: 213
References: 62
Citations by year: 2026: 8 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 12 · 2017: 9 · 2016: 20 · 2015: 13 · 2014: 13 · 2013: 20 · 2012: 15
FWCI: 12.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (P01HL046403, HL87062, R37HL087062, R01HL080702, HL-46403)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK045462, DK 45462)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: tetrahydrobiopterin, 7,8-dihydrobiopterin, eNOS uncoupling, nitric oxide production, superoxide production, endothelial cells, hyperglycemia, type 2 diabetes, BH4 supplementation, calcium ionophore, Zucker diabetic fatty rats
MeSH terms: Animals, Biopterins, Blood Glucose, Cell Line, Diabetes Mellitus, Type 2, Disease Models, Animal, Enzyme Inhibitors, Glucose, Glutathione, Mitochondria, Nitric Oxide, Oxidation-Reduction, Protein Binding, Rats, Zucker, Superoxides, Time Factors, Tritium, NG-Nitroarginine Methyl Ester, Endothelial Cells, Mice, Rats, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III

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Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS

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