ArticleScientific reports2020
Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease.
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 11 papers.
What it found
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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
11 citing papers in PubMed, 15 citations in OpenAlex.
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- Tumor Microenvironment-Responsive Nanoparticles Enhance IDO1 Blockade Immunotherapy by Remodeling Metabolic Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NO/NOS system dysregulation as a key molecular mechanism in chemotherapy-induced cardiotoxicity: a review.Frontiers in cardiovascular medicine · 2025Review
- OptimizingFrontiers in cell and developmental biology · 2025Article
- Nitric oxide inhibits FTO demethylase activity to regulate NRedox biology · 2023Article
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Inactivation of soluble guanylyl cyclase in living cells proceeds without loss of haem and involves heterodimer dissociation as a common step.British journal of pharmacology · 2022Article
- The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms.Scientific reports · 2022Article
- The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.Scientific reports · 2018Article
- Maturation, inactivation, and recovery mechanisms of soluble guanylyl cyclase.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase and exogenous NO from NO donor compounds decreased sGC protein and activity. This effect was not mediated by cGMP as the NO-independent sGC stimulator, or direct activation of cGMP-dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in-vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC while leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formation.
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Registered trials
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