ArticleFree radical biology & medicine2012
Preserving mitochondrial function prevents the proteasomal degradation of GTP cyclohydrolase I.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01825369 (Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow), which is not on this map. Cited by 17 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.
Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow
Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
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- Tetrahydrobiopterin induces proteasome inhibitor resistance and tumor progression in multiple myeloma.Medical oncology (Northwood, London, England) · 2022Article
- Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.Scientific reports · 2020Article
- Gender Difference in Damage-Mediated Signaling Contributes to Pulmonary Arterial Hypertension.Antioxidants & redox signaling · 2019Article
- Caffeine ameliorates hyperoxia-induced lung injury by protecting GCH1 function in neonatal rat pups.Pediatric research · 2017Article
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- Asymmetric Dimethylarginine Stimulates Akt1 Phosphorylation via Heat Shock Protein 70-Facilitated Carboxyl-Terminal Modulator Protein Degradation in Pulmonary Arterial Endothelial Cells.American journal of respiratory cell and molecular biology · 2016Article
- Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.PloS one · 2016Article
- The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression.Molecular cancer research : MCR · 2015Article
- The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype.Pulmonary circulation · 2015Article
- The NO/ONOO-cycle as the central cause of heart failure.International journal of molecular sciences · 2013Review
- L-carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow.Pediatric research · 2013Article
- Reactive oxygen species in pulmonary vascular remodeling.Comprehensive Physiology · 2013Review
- Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow.Journal of cellular biochemistry · 2013Article
- PPAR-γ regulates carnitine homeostasis and mitochondrial function in a lamb model of increased pulmonary blood flow.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The development of pulmonary hypertension is a common accompaniment of congenital heart disease (CHD) with increased pulmonary blood flow. Our recent evidence suggests that asymmetric dimethylarginine (ADMA)-induced mitochondrial dysfunction causes endothelial nitric oxide synthase (eNOS) uncoupling secondary to a proteasome-dependent degradation of GTP cyclohydrolase I (GCH1) that results in a decrease in the NOS cofactor tetrahydrobiopterin (BH(4)). Decreases in NO signaling are thought to be an early hallmark of endothelial dysfunction. As l-carnitine plays an important role in maintaining mitochondrial function, in this study we examined the protective mechanisms and the therapeutic potential of l-carnitine on NO signaling in pulmonary arterial endothelial cells and in a lamb model of CHD and increased pulmonary blood flow (Shunt). Acetyl-l-carnitine attenuated the ADMA-mediated proteasomal degradation of GCH1. This preservation was associated with a decrease in the association of GCH1 with Hsp70 and the C-terminus of Hsp70-interacting protein (CHIP) and a decrease in its ubiquitination. This in turn prevented the decrease in BH(4) levels induced by ADMA and preserved NO signaling. Treatment of Shunt lambs with l-carnitine also reduced GCH1/CHIP interactions, attenuated the ubiquitination and degradation of GCH1, and increased BH(4) levels compared to vehicle-treated Shunt lambs. The increases in BH(4) were associated with decreased NOS uncoupling and enhanced NO generation. Thus, we conclude that L-carnitine may have a therapeutic potential in the treatment of pulmonary hypertension in children with CHD with increased pulmonary blood flow.
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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.