Role of increased guanosine triphosphate cyclohydrolase-1 expression and tetrahydrobiopterin levels upon T cell activation
Open accessAbstract
Tetrahydrobiopterin (BH(4)) is an essential co-factor for the nitric-oxide (NO) synthases, and in its absence these enzymes produce superoxide (O(2)(·-)) rather than NO. The rate-limiting enzyme for BH(4) production is guanosine triphosphate cyclohydrolase-1 (GTPCH-1). Because endogenously produced NO affects T cell function, we sought to determine whether antigen stimulation affected T cell GTPCH-1 expression and ultimately BH(4) levels. Resting T cells had minimal expression of inducible NOS (NOS2), endothelial NOS (NOS3), and GTPCH-1 protein and nearly undetectable levels of BH(4). Anti-CD3 stimulation of T cells robustly stimulated the coordinated expression of NOS2, NOS3, and GTPCH-1 and markedly increased both GTPCH-1 activity and T cell BH(4) levels. The newly expressed GTPCH-1 was phosphorylated on serine 72 and pharmacological inhibition of casein kinase II reduced GTPCH-1 phosphorylation and blunted the increase in T cell BH(4). Inhibition of GTPCH-1 with diaminohydroxypyrimidine (1 mmol/liter) prevented T cell BH(4) accumulation, reduced NO production, and increased T cell O(2)(·-) production, due to both NOS2 and NOS3 uncoupling. GTPCH-1 inhibition also promoted TH(2) polarization in memory CD4 cells. Ovalbumin immunization of mice transgenic for an ovalbumin receptor (OT-II mice) confirmed a marked increase in T cell BH(4) in vivo. These studies identify a previously unidentified consequence of T cell activation, promoting BH(4) levels, NO production, and modulating T cell cytokine production.
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GCH1 is expressed in T cells but only after TCR stimulation.
“We and others have shown that GCH1 is expressed in T cells but only after TCR stimulation (Chen et al., 2011; Cronin et al., 2018).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Chen et al., 2011
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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 · see citing works
Self-citationLandmesser, 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 · see citing works
Barnden, M., Allison, J., Heath, W. R., & Carbone, F. (1998) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.1998.00709.x · Cited by 1,491 · see citing works
Tetrahydrobiopterin biosynthesis, regeneration and functions
Thöny, B., Auerbach, G., & Blau, N. (2000) · Biochemical Journal · doi:10.1042/bj3470001 · Cited by 867 · see citing works
Generation of superoxide by purified brain nitric oxide synthase
Pou, S., Pou, W. S., Bredt, D. S., Snyder, S. H., & Rosen, G. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35745-4 · Cited by 750 · see citing works
Tzima, E., del Pozo, M. Á., Shattil, S. J., Chien, S., & Schwartz, M. A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4639 · Cited by 571 · see citing works
STRUCTURE-FUNCTION ASPECTS IN THE NITRIC OXIDE SYNTHASES
Stuehr, D. J. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.339 · Cited by 547 · see citing works
Measurement of Reactive Oxygen Species in Cardiovascular Studies
Dikalov, S., Griendling, K. K., & Harrison, D. G. (2007) · Hypertension · doi:10.1161/01.hyp.0000258594.87211.6b · Cited by 532 · see citing works
Self-citationCa2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase
Heinzel, B., John, M., Klatt, P., Böhme, E., & Mayer, B. (1992) · Biochemical Journal · doi:10.1042/bj2810627 · Cited by 530 · see citing works
T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation
Jackson, S. H., Devadas, S., Kwon, J., Pinto, L. A., & Williams, M. S. (2004) · Nature Immunology · doi:10.1038/ni1096 · Cited by 457 · see citing works
Gross, S. S., & Levi, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35667-9 · Cited by 443 · see citing works
Nitric Oxide and Cyclic GMP in Cell Signaling and Drug Development
Murad, F. (2006) · New England Journal of Medicine · doi:10.1056/nejmsa063904 · Cited by 420 · see citing works
Sarno, S., Reddy, H., Meggio, F., Ruzzene, M., Davies, S. P., Donella‐Deana, A., Shugar, D., & Pinna, L. A. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02404-8 · Cited by 356 · see citing works
Wever, R. M. F., van Dam, T., van Rijn, H. J. M., de Groot, F. G., & Rabelink, T. J. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7069 · Cited by 281 · see citing works
Channon, K. M. (2004) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2004.10.003 · Cited by 196 · see citing works
Tetrahydrobiopterin Radical Enzymology
Wei, C.-C., Crane, B. R., & Stuehr, D. J. (2003) · Chemical Reviews · doi:10.1021/cr0204350 · Cited by 175 · see citing works
Niedbala, W., Cai, B., Liu, H., Pitman, N., Chang, L., & Liew, F. Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703725104 · Cited by 156 · see citing works
Niedbała, W., Wei, X., Campbell, C., Thomson, D., Komai‐Koma, M., & Liew, F. Y. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252464599 · Cited by 143 · see citing works
Oxidative Stress Promotes Polarization of Human T Cell Differentiation Toward a T Helper 2 Phenotype
King, M. R., Ismail, A. S., Davis, L. S., & Karp, D. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.5.2765 · Cited by 132 · see citing works
Wei, C., Wang, Z., Wang, Q., Meade, A. L., Hemann, C. F., Hille, R., & Stuehr, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008441200 · Cited by 129 · see citing works
Benbernou, N., Esnault, S. J., Shin, H. C. K., Fekkar, H., & Guenounou, M. (1997) · Immunology · doi:10.1046/j.1365-2567.1997.00260.x · Cited by 124 · see citing works
Inducible nitric oxide synthase in T cells regulates T cell death and immune memory
Vig, M., Srivastava, S., Kandpal, U., Sade, H., Lewis, V., Sarin, A., George, A., Bal, V., Durdik, J. M., & Rath, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20225 · Cited by 118 · see citing works
Regulation of Tetrahydrobiopterin Biosynthesis by Shear Stress
Widder, J. D., Chen, W., Li, L., Dikalov, S., Thöny, B., Hatakeyama, K., & Harrison, D. G. (2007) · Circulation Research · doi:10.1161/circresaha.107.153809 · Cited by 114 · see citing works
Patel, K. B., Stratford, M. R. L., Wardman, P., & Everett, S. A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00777-8 · Cited by 95 · see citing works
Lck is a key target of imatinib and dasatinib in T-cell activation
Lee, K. C., Ouwehand, I., Giannini, A. L. M., Thomas, N. S. B., Dibb, N. J., & Bijlmakers, M.-J. (2010) · Leukemia · doi:10.1038/leu.2010.11 · Cited by 91 · see citing works
Self-Limitation of Th1-Mediated Inflammation by IFN-γ
Feuerer, M., Eulenburg, K., Loddenkemper, C., Hamann, A., & Huehn, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.5.2857 · Cited by 85 · see citing works
G�l, E. M., Nelson, J. M., & Sherman, A. D. (1978) · Neurochemical Research · doi:10.1007/bf00964361 · Cited by 84 · see citing works
Endothelial Nitric Oxide Synthase Regulates T Cell Receptor Signaling at the Immunological Synapse
Ibiza, S., Víctor, V. M., Boscá, I., Ortega, Á., Urzainqui, A., O’Connor, J., Sánchez‐Madrid, F., Esplugues, J. V., & Serrador, J. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.04.006 · Cited by 80 · see citing works
Ibiza, S., Pérez-Rodríguez, A., Ortega, Á., Martı́nez-Ruiz, A., Barreiro, O., García-Domínguez, C. A., Víctor, V. M., Esplugues, J. V., Rojas, J. M., Sánchez‐Madrid, F., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711062105 · Cited by 78 · see citing works
Yoneyama, T., & Hatakeyama, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20102 · Cited by 75 · see citing works
Catalytic Reduction of a Tetrahydrobiopterin Radical within Nitric-oxide Synthase
Wei, C., Wang, Z., Tejero, J., Yang, Y., Hemann, C. F., Hille, R., & Stuehr, D. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709250200 · Cited by 74 · see citing works
Tai, L.-K., Okuda, M., Abe, J., Chen, Y., & Berk, B. C. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000034475.40227.40 · Cited by 74 · see citing works
Li, L., Rezvan, A., Salerno, J. C., Husain, A., Kwon, K., Jo, H., Harrison, D. G., & Chen, W. (2009) · Circulation Research · doi:10.1161/circresaha.109.210658 · Cited by 63 · see citing works
Suppression of Regulatory T Cells by IL-12p40 Homodimer via Nitric Oxide
Brahmachari, S., & Pahan, K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0800276 · Cited by 61 · see citing works
Zhu, Y., Nikolic, D. S., van Breemen, R. B., & Silverman, R. B. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0445645 · Cited by 47 · see citing works
Miller, A. A., Megson, I. L., & Gray, G. A. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703528 · Cited by 42 · see citing works
Collins, M., Tremblay, M. M., Chapman, N. M., Curtiss, M. L., Rothman, P. B., & Houtman, J. C. D. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0409227 · Cited by 32 · see citing works
Collins, M., Bartelt, R. R., & Houtman, J. C. D. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.03.009 · Cited by 27 · see citing works
Inhibition of Pyk2 Blocks Airway Inflammation and Hyperresponsiveness in a Mouse Model of Asthma
Duan, Y., Learoyd, J., Meliton, A. Y., Clay, B. S., Leff, A. R., & Zhu, X. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0469oc · Cited by 27 · see citing works
Tóth, M., Kukor, Z., & Sahin‐Tóth, M. (1997) · Placenta · doi:10.1016/s0143-4004(97)90092-8 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Ibiza, S., Pe ´rez-Rodríguez, A., Ortega, A., Martínez-Ruiz, A., Barreiro, O., García-Domínguez, C. A., Víctor, V. M., Esplugues, J. V., Rojas, J. M., Sa ´nchez-Madrid, F., and Serrador, J. M. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 10507-10512
- Niedbala, W., Cai, B., Liu, H., Pitman, N., Chang, L., and Liew, F. Y. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 15478 -15483
- Cai, H., Dikalov, S., Griendling, K. K., and Harrison, D. G. (2005) in Meth- ods in Molecular Medicine (Sreejayan, N., and Ren, J. eds) pp. 293-314, Humana Press, New York, NY
- Niedbala, W., Wei, X. Q., Campbell, C., Thomson, D., Komai-Koma, M., and Liew, F. Y. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 16186 -16191
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“We and others have shown that GCH1 is expressed in T cells but only after TCR stimulation (Chen et al., 2011; Cronin et al., 2018).”
BackgroundThe metabolite BH4 controls T cell proliferation in autoimmunity and cancer
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“In whole cell and body systems iNOS uncoupling is observed, with reduced BH4 causing increased iNOS uncoupling in T-cells and in renal allografts associated with a BH4-inhibitable superoxide production [34,35].”
BackgroundŁuczak, A., Madej, M., Kasprzyk, A., & Doroszko, A. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1417981 · Cited by 90 · see citing works
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Spurlock, C. F., Gass, H. M., Bryant, C. J., Wells, B. C., Olsen, N. J., & Aune, T. M. (2014) · Rheumatology · doi:10.1093/rheumatology/keu279 · Cited by 68 · see citing works
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- Authors
- Chen, W., Li, L., Brod, T., Saeed, O., Thabet, S., Jansen, T., Dikalov, S., Weyand, C., Goronzy, J., & Harrison, D. G.
- Affiliations
- Emory University (US)
- Stanford Medicine (US)
- Corresponding author
- Harrison, David G.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 286
- Issue
- 16
- Pages
- 13846-13851
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3077585
- OpenAlex
- W1989089149
- Cited by
- 36
- References
- 39
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 7 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2012: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Institute of Allergy and Infectious Diseases (R01AI044142, R01AI108906, R56AI044142)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- tetrahydrobiopterin, T cell activation, nitric oxide synthase, nitric oxide, superoxide, casein kinase 2, Th2 polarization, memory CD4+ T cells, anti-CD3 stimulation, ovalbumin immunization
- MeSH terms
- Animals, Biopterins, GTP Cyclohydrolase, Humans, Immunologic Memory, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Oxygen, Phosphorylation, T-Lymphocytes, Gene Expression Regulation, Enzymologic, Cytokines, CD3 Complex, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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