ArticleDiabetes2013
Peroxynitrite-dependent zinc release and inactivation of guanosine 5'-triphosphate cyclohydrolase 1 instigate its ubiquitination in diabetes.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 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
13 citing papers in PubMed, 24 citations in OpenAlex.
- An Overexpression of SLC30A6 Gene Contributes to Cardiomyocyte Dysfunction via Affecting Mitochondria and Inducing Activations in K-Acetylation and Epigenetic Proteins.Biochemical genetics · 2024Article
- Citronellal improves endothelial dysfunction by affecting the stability of the GCH1 protein.Acta biochimica et biophysica Sinica · 2024Article
- Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.Antioxidants & redox signaling · 2021Review
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
- Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?International journal of molecular sciences · 2019Review
- Nicotine induces endothelial dysfunction and promotes atherosclerosis via GTPCH1.Journal of cellular and molecular medicine · 2018Article
- Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling.Scientific reports · 2017Article
- Inhibition of Aberrant MicroRNA-133a Expression in Endothelial Cells by Statin Prevents Endothelial Dysfunction by Targeting GTP Cyclohydrolase 1 in Vivo.Circulation · 2016Article
- Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.Free radical biology & medicine · 2016Article
- Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
- Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase.The EMBO journal · 2015Article
- Modulation of Radiation Response by the Tetrahydrobiopterin Pathway.Antioxidants (Basel, Switzerland) · 2015Review
- Redox regulation of endothelial cell fate.Cellular and molecular life sciences : CMLS · 2014Article
Corrections and comments
- Retraction · 2023-05-15Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Aberrant degradation of guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) with consequent deficiency of tetrahydrobiopterin is considered the primary cause for endothelial dysfunction in diabetes. How GTPCH1 becomes susceptible to the degradation remains unknown. We hypothesized that oxidation and release of the zinc ion by peroxynitrite (ONOO(-)), a potent oxidant generated by nitric oxide and superoxide anions, instigates GTPCH1 ubiquitination and degradation. Zinc contents, GTPCH1 ubiquitination, and GTPCH1 activity were assayed in purified GTPCH1, endothelial cells, and hearts from diabetic mice. Exogenous ONOO(-) dose-dependently released zinc, inhibited its activity, and increased the ubiquitin binding affinity of GTPCH1 in vitro and in endothelial cells. Consistently, high glucose (30 mmol/L) inhibited GTPCH1 activity with increased ubiquitination, which was inhibited by antioxidants. Furthermore, mutation of the zinc-binding cysteine (141) (C141R or C141A) significantly reduced GTPCH1 activity and reduced its half-life but increased GTPCH1 ubiquitination, indicating an essential role of the zinc ion in maintaining the catalytic activity and stability of GTPCH1. Finally, GTPCH1 ubiquitination and degradation markedly increased in parallel with decreased GTPCH1 activity in the aortas and hearts of diabetic mice, both of which were attenuated by the inhibitors of ONOO(-) in mice in vivo. Taken together, we conclude that ONOO(-) releases zinc and inhibits GTPCH1, resulting in its ubiquitination and degradation of the enzyme.
Indexed as
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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.