ArticleScientific reports2020
CR6-interacting factor 1 deficiency reduces endothelial nitric oxide synthase activity by inhibiting biosynthesis of tetrahydrobiopterin.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- The Effect of the MTHFR C677T Genotype Polymorphism on the Efficacy of Folic Acid Treatment for Hyperhomocysteinemia and Cardiovascular Endothelial Function.Chronic diseases and translational medicine · 2026Article
- Protective Effects of CR6-Interacting Factor 1 Against Angiotensin II-Induced Atrial Fibrillation by Regulating the SIRT1/eNOS Signaling Pathway and Cardiomyocyte Remodeling.Journal of inflammation research · 2026Article
- GADD45GIP1 promotes osteosarcoma progression by modulating RPL35 ubiquitination and alleviating endoplasmic reticulum stress via the PERK/eIF2α pathway.Cancer cell international · 2025Article
- Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Cardiovascular aging: spotlight on mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Review
- Sodium-Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Review
- Analysis of yellow mutant rainbow trout transcriptomes at different developmental stages reveals dynamic regulation of skin pigmentation genes.Scientific reports · 2022Article
- Multifunctions of CRIF1 in cancers and mitochondrial dysfunction.Frontiers in oncology · 2022Review
- CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Novel Role of GPR35 (G-Protein-Coupled Receptor 35) in the Regulation of Endothelial Cell Function and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Interplay Between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease.Antioxidants & redox signaling · 2021Review
- Nebivolol combined with tetrahydrobiopterin affects diastolic function in spontaneously hypertensive rats via the nitric oxide/cyclic guanosine monophosphate signalling pathway.BMC pharmacology & toxicology · 2020Article
- Topical Donepezil for Cholinergic Modulation in Chronic Wound Repair.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair SocietyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Downregulation of CR6 interacting factor 1 (CRIF1) has been reported to induce mitochondrial dysfunction, resulting in reduced activity of endothelial nitric oxide synthase (eNOS) and NO production in endothelial cells. Tetrahydrobiopterin (BH4) is an important cofactor in regulating the balance between NO (eNOS coupling) and superoxide production (eNOS uncoupling). However, whether the decreased eNOS and NO production in CRIF1-deficient cells is associated with relative BH4 deficiency-induced eNOS uncoupling remains completely unknown. Our results showed that CRIF1 deficiency increased eNOS uncoupling and depleted levels of total biopterin and BH4 by reducing the enzymes of BH4 biosynthesis (GCH-1, PTS, SPR, and DHFR) in vivo and vitro, respectively. Supplementation of CRIF1-deficient cells with BH4 significantly increased the recovery of Akt and eNOS phosphorylation and NO synthesis. In addition, scavenging ROS with MitoTEMPO treatment replenished BH4 levels by elevating levels of GCH-1, PTS, and SPR, but with no effect on the level of DHFR. Downregulation of DHFR synthesis regulators p16 or p21 in CRIF1-deficient cells partially recovered the DHFR expression. In summary, CRIF1 deficiency inhibited BH4 biosynthesis and exacerbated eNOS uncoupling. This resulted in reduced NO production and increased oxidative stress, which contributes to endothelial dysfunction and is involved in the pathogenesis of cardiovascular diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.