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Quantitative Regulation of Intracellular Endothelial Nitric-oxide Synthase (eNOS) Coupling by Both Tetrahydrobiopterin-eNOS Stoichiometry and Biopterin Redox Status
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Tetrahydrobiopterin (BH4) is a critical determinant of endothelial nitric-oxide synthase (eNOS) activity. In the absence of BH4, eNOS becomes "uncoupled" and generates superoxide rather than NO. However, the stoichiometry of intracellular BH4/eNOS interactions is not well defined, and it is unclear whether intracellular BH4 deficiency alone is sufficient to induce eNOS uncoupling. To address these questions, we developed novel cell lines with tet-regulated expression of human GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in BH4 synthesis, to selectively induce intracellular BH4 deficiency by incubation with doxycycline. These cells were stably co-transfected to express a human eNOS-green fluorescent protein fusion protein, selecting clones expressing either low (GCH/eNOS-LOW) or high (GCH/eNOS-HIGH) levels. Doxycycline abolished GTPCH mRNA expression and GTPCH protein, leading to markedly diminished total biopterin levels and a decreased ratio of BH4 to oxidized biopterins in cells expressing eNOS. Intracellular BH4 deficiency induced superoxide generation from eNOS, as assessed by N-nitro-L-arginine methyl ester inhibitable 2-hydroxyethidium generation, and attenuated NO production. Quantitative analysis of cellular BH4 versus superoxide production between GCH/eNOS-LOW and GCH/eNOS-HIGH cells revealed a striking linear relationship between eNOS protein and cellular BH4 stoichiometry, with eNOS uncoupling at eNOS:BH4 molar ratio >1. Furthermore, increasing the intracellular BH2 concentration in the presence of a constant eNOS:BH4 ratio was sufficient to induce eNOS-dependent superoxide production. This specific, reductionist approach in a cell-based system reveals that eNOS:BH4 reaction stoichiometry together with the intracellular BH4:BH2 ratio, rather than absolute concentrations of BH4, are the key determinants of eNOS uncoupling, even in the absence of exogenous oxidative stress.
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“Thus, not only is the NO synthesis completely abolished but the protein also becomes an oxidase, generating superoxide instead of NO (191, 972, 1007) (Table 6).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [191]
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“Mechanistically, when NOS binds BH2 instead of BH4, the ferrous/oxy heme cannot hydroxylate l-arginine to NG-hydroxy-l-arginine, NO synthesis is blocked, and the oxygen is eventually oxidized to superoxide.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [191]
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Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
The reaction of NO with superoxide
Huie, R. E., & Padmaja, S. (1993) · Free Radical Research Communications · doi:10.3109/10715769309145868 · Cited by 2,121
Hypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
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
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
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
Methods in Nitric Oxide Research
Young, J. (1997) · Physiological Measurement · doi:10.1088/0967-3334/18/1/008 · Cited by 749
Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols
Kuzkaya, N., Weissmann, N., Harrison, D. G., & Dikalov, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302227200 · Cited by 692
Superoxide and peroxynitrite inatherosclerosis.
White, C. R., Brock, T. A., Chang, L. Y., Crapo, J. D., BRISCOE, P. M., Ku, D. D., Bradley, W. A., Gianturco, S. H., Gore, J. Z., & Freeman, B. Α. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.3.1044 · Cited by 684
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Current Mechanistic Concepts in Ischemia and Reperfusion Injury
Wu, M., Yiang, G.-T., Liao, W.-T., Tsai, A. P., Cheng, Y., Cheng, P., Li, C.-Y., & Li, C. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000489241 · Cited by 1,401
Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes
Shah, M. S., & Brownlee, M. (2016) · Circulation Research · doi:10.1161/circresaha.116.306923 · Cited by 609
Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review
Wang, W., Zhou, H., & Liu, L. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.027 · Cited by 565
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Targeting vascular (endothelial) dysfunction
Daiber, A., Steven, S., Weber, A., Shuvaev, V. V., Muzykantov, V. R., Laher, I., Li, H., Lamas, S., & Münzel, T. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13517 · Cited by 501
eNOS uncoupling and endothelial dysfunction in aged vessels
Yang, Y., Huang, A., Kaley, G., & Sun, D. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00230.2009 · Cited by 381
Janaszak-Jasiecka, A., Płoska, A., Wierońska, J. M., Dobrucki, L. W., & Kalinowski, L. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00423-2 · Cited by 358
Daiber, A., Xia, N., Steven, S., Oelze, M. W., Hanf, A., Kröller‐Schön, S., Münzel, T. F., & Li, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010187 · Cited by 322
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Cronin, S. J. F., Seehus, C., Weidinger, A., Talbot, S., Reissig, S., Seifert, M., Pierson, Y., McNeill, E., Longhi, M. S., Turnes, B. L., et al. (2018) · Nature · doi:10.1038/s41586-018-0701-2 · Cited by 285
Self-citationMonoamine neurotransmitter disorders—clinical advances and future perspectives
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Tetrahydrobiopterin in Cardiovascular Health and Disease
Bendall, J. K., Douglas, G., McNeill, E., Channon, K. M., & Crabtree, M. J. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5566 · Cited by 231
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Self-citationAntoniades, C., Bakogiannis, C., Leeson, P., Guzik, T. J., Zhang, M.-H., Tousoulis, D., Antonopoulos, A. S., Demosthenous, M., Marinou, K., Hale, A., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.985150 · Cited by 219
Self-citationKietadisorn, R., Juni, R. P., & Moens, A. L. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00540.2011 · Cited by 221
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Self-citationGoveia, J., Stapor, P. C., & Carmeliet, P. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404156 · Cited by 203
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Reactive oxygen and nitrogen species in pulmonary hypertension
Tabima, D. M., Frizzell, S. A., & Gladwin, M. T. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.041 · Cited by 194
Resveratrol Reverses Endothelial Nitric-Oxide Synthase Uncoupling in Apolipoprotein E Knockout Mice
Xia, N., Daiber, A., Habermeier, A., Closs, E. I., Thum, T., Spanier, G., Lü, Q., Oelze, M. W., Torzewski, M., Lackner, K. J., et al. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.168724 · Cited by 186
Modulation of endothelial nitric oxide by plant-derived products
Schmitt, C. A., & Dirsch, V. M. (2009) · Nitric Oxide · doi:10.1016/j.niox.2009.05.006 · Cited by 177
Cunnington, C., Van Assche, T., Shirodaria, C., Kylintireas, I., Lindsay, A. C., Lee, J. M., Antoniades, C., Margaritis, M., Lee, R., Cerrato, R., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.038919 · Cited by 166
Self-citationNitric Oxide Synthases in Heart Failure
Carnicer, R., Crabtree, M. J., Sivakumaran, V., Casadei, B., & Kass, D. A. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4824 · Cited by 170
Self-citationEffects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles
Sindler, A. L., Delp, M. D., Reyes, R., Wu, G., & Muller‐Delp, J. M. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.172221 · Cited by 158
Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies
on behalf of the International Working Group on Neurotransmitter related Disorders (iNTD), Opladen, T., López‐Laso, E., Cortès‐Saladelafont, E., Pearson, T. S., Hs, S., Yıldız, Y., Assmann, B. E., Kurian, M. A., Leuzzi, V., et al. (2020) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-020-01379-8 · Cited by 165
McNeill, E., Crabtree, M. J., Sahgal, N., Patel, J., Chuaiphichai, S., Iqbal, A. J., Hale, A., Greaves, D. R., & Channon, K. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.575 · Cited by 150
Self-citationReactive oxygen species in hypertension
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Csonka, C., Páli, T., Bencsik, P., Görbe, A., Ferdinándy, P., & Csont, T. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12832 · Cited by 150
Roles of oxidative stress and redox regulation in atherosclerosis.
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Kalyanaraman, B., Dranka, B. P., Hardy, M., Michalski, R., & Zielonka, J. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.05.008 · Cited by 120
Douglas, G., Bendall, J. K., Crabtree, M. J., Tatham, A. L., Carter, E. E., Hale, A. B., & Channon, K. M. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs026 · Cited by 111
Self-citationMcNulty, H., Strain, J., Hughes, C., & Ward, M. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.10.002 · Cited by 111
Chalupský, K., Kračun, D., Kanchev, I., Bertram, K., & Görlach, A. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6329 · Cited by 103
Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy
Zhang, Y., Janssens, S. P., Wingler, K., Schmidt, H. H. H. W., & Moens, A. L. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01315.2010 · Cited by 99
Sugiyama, T., Levy, B. D., & Michel, T. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809295200 · Cited by 94
Heiß, E. H., Schachner, D., Werner, E. R., & Dirsch, V. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.009175 · Cited by 89
Łuczak, A., Madej, M., Kasprzyk, A., & Doroszko, A. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1417981 · Cited by 95
Crabtree, M. J., Brixey, R., Batchelor, H., Hale, A. B., & Channon, K. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415992 · Cited by 83
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Self-citationLatrémolière, A., & Costigan, M. (2011) · Current Pharmaceutical Biotechnology · doi:10.2174/138920111798357393 · Cited by 76
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Wang, W.-L., Shih, Y.-T., Wei, S.-Y., & Chiu, J.-J. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01177-z · Cited by 50
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Mollace, R., Scarano, F., Bava, I., Carresi, C., Maiuolo, J., Tavernese, A., Gliozzi, M., Musolino, V., Muscoli, S., Palma, E., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106931 · Cited by 48
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Self-citationXu, C., Tang, F., Lü, M., Yang, J., Han, R., Mei, M., Hu, J., Zhou, M.-S., & Wang, H. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.02.009 · Cited by 45
Ohashi, A., Sugawara, Y., Mamada, K., Harada, Y., Sumi, T., Anzai, N., Aizawa, S., & Hasegawa, H. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2010.09.005 · Cited by 45
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Lopez, M., Lax, A., Vicente, Á. H., Guillen, E. S., Hernández-Martínez, A. M., del Palacio, M. J. F., Bayés‐Genís, A., & Pascual-Figal, D. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-70454-8 · Cited by 37
Li, H., Förstermann, U., Xia, N., Kuntić, M., Münzel, T. F., & Daiber, A. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.06.009 · Cited by 38
Yan, S., Resta, T. C., & Jernigan, N. L. (2020) · Antioxidants · doi:10.3390/antiox9100999 · Cited by 38
de Melo, F. H. M., Molognoni, F., Morais, A. S., Toricelli, M., Mouro, M. G., Higa, E. M. S., Lopes, J. D., & Jasiulionis, M. G. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.02.022 · Cited by 36
Psara, E., Pentieva, K. D., Ward, M., & McNulty, H. (2020) · Biochimie · doi:10.1016/j.biochi.2020.03.016 · Cited by 35
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Gao, L., Pung, Y. F., Zhang, J., Chen, P., Wang, T., Li, M., Meza, M. A., Toro, L., & Cai, H. “. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00007.2009 · Cited by 33
Ryan, B. J., Venda, L. L., Crabtree, M. J., Hale, A., Channon, K. M., & Wade‐Martins, R. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.008 · Cited by 32
Self-citationMcNulty, H., Strain, J., Hughes, C., Pentieva, K. D., & Ward, M. (2019) · Current Developments in Nutrition · doi:10.1093/cdn/nzz102 · Cited by 31
Dikalova, A., Aschner, J. L., Kaplowitz, M. R., Summar, M. L., & Fike, C. D. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00238.2016 · Cited by 29
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Chuaiphichai, S., Rashbrook, V. S., Hale, A., Trelfa, L., Patel, J., McNeill, E., Lygate, C. A., Channon, K. M., & Douglas, G. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11144 · Cited by 28
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Mu, W., Hu, N., Zhang, L.-H., Jiang, W., Yan, T., Zhang, T., Liu, A., Zhang, Y., Zhao, J., Shi, L., et al. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154146 · Cited by 25
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Metadata
- Authors
- Crabtree, M. J., Tatham, A. L., Al-Wakeel, Y., Warrick, N., Hale, A. B., Cai, S., Channon, K. M., & Alp, N. J.
- Affiliations
- John Radcliffe Hospital (GB)
- Corresponding author
- Alp, Nicholas J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 284
- Issue
- 2
- Pages
- 1136-1144
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2069153850
- Cited by
- 200
- References
- 40
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 13 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 18 · 2013: 15 · 2012: 14
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (GR074428/Z/04/Z)
- British Heart Foundation (PG/05/141/20098, RG/02/006, RG/07/003/23133)
- 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 › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- endothelial nitric oxide synthase, tetrahydrobiopterin, eNOS uncoupling, GTP cyclohydrolase I, superoxide production, nitric oxide production, doxycycline, oxidative stress
- MeSH terms
- Animals, Biopterins, Cell Line, GTP Cyclohydrolase, Humans, Nitric Oxide, Oxidation-Reduction, Protein Binding, Superoxides, RNA, Small Interfering, Mice, Nitric Oxide Synthase Type III
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