ArticleThe Journal of biological chemistry2011
Role of increased guanosine triphosphate cyclohydrolase-1 expression and tetrahydrobiopterin levels upon T cell activation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Ferroptosis as a new tool for tumor suppression through lipid peroxidation.Communications biology · 2024Review
- Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer.Frontiers in molecular biosciences · 2024Article
- BH4 supplementation reduces retinal cell death in ischaemic retinopathy.Scientific reports · 2023Article
- Early detection and metabolic pathway identification of T cell activation by in-process intracellular mass spectrometry.Cytotherapy · 2023Article
- Crosstalk between trace elements and T-cell immunity during early-life health in pigs.Science China. Life sciences · 2023Review
- Infiltration of Tumors Is Regulated by T cell-Intrinsic Nitric Oxide Synthesis.Cancer immunology research · 2023Article
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- The metabolic recovery of marathon runners: an untargetedFrontiers in physiology · 2023Article
- Biopterin metabolism and nitric oxide recoupling in cancer.Frontiers in oncology · 2023Review
- Marginal BH4 deficiencies, iNOS, and self-perpetuating oxidative stress in post-acute sequelae of Covid-19.Medical hypotheses · 2022Article
- The Redox-Metabolic Couple of T Lymphocytes: Potential Consequences for Hypertension.Antioxidants & redox signaling · 2021Review
- Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases.Oxidative medicine and cellular longevity · 2020Review
- The Role of Iron Regulation in Immunometabolism and Immune-Related Disease.Frontiers in molecular biosciences · 2019Review
- Article
- Oxidative Stress and Hypertensive Diseases.The Medical clinics of North America · 2017Review
- Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation.Free radical biology & medicine · 2015Article
- Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes.Rheumatology (Oxford, England) · 2015Article
- Immune-mediated vascular injury and dysfunction in transplant arteriosclerosis.Frontiers in immunology · 2014Review
- Nitrosothiols in the immune system: signaling and protection.Antioxidants & redox signaling · 2013Review
- The role of tetrahydrobiopterin in inflammation and cardiovascular disease.Thrombosis and haemostasis · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.