ArticleThe Journal of biological chemistry2009
Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 75 citations in OpenAlex.
- Snake Toxins Affecting Blood Vessel Walls: Mode of Action and Biological Significance.International journal of molecular sciences · 2025Review
- Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Regulation of urea cycle by reversible high-stoichiometry lysine succinylation.Nature metabolism · 2024Article
- Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (<EDGPIPP) fromThe journal of venomous animals and toxins including tropical diseases · 2024Article
- Snake Venom Components as Therapeutic Drugs in Ischemic Heart Disease.Biomolecules · 2023Review
- Circulating metabolites modulated by diet are associated with depression.Molecular psychiatry · 2023Article
- Dietary supplements and vascular function in hypertensive disorders of pregnancy.Pflugers Archiv : European journal of physiology · 2023Review
- BmooMPα-I, a Metalloproteinase Isolated fromToxins · 2022Article
- Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1.EMBO reports · 2021Article
- Implications of SARS-Cov-2 infection on eNOS and iNOS activity: Consequences for the respiratory and vascular systems.Nitric oxide : biology and chemistry · 2021Review
- Integrated Metabolomics and Transcriptomics Analysis of Monolayer and Neurospheres from Established Glioblastoma Cell Lines.Cancers · 2021Article
- Snake venom-derived bradykinin-potentiating peptides: A promising therapy for COVID-19?Drug development research · 2021Review
- Clinical assessment and pathophysiology ofThe journal of venomous animals and toxins including tropical diseases · 2020Article
- Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function.Immunity · 2019Article
- Hypotensive Snake Venom Components-A Mini-Review.Molecules (Basel, Switzerland) · 2019Review
- Decreased serum L-arginine and L-citrulline levels in major depression.Psychopharmacology · 2017Article
- Argininosuccinate synthase 1 is an intrinsic Akt repressor transactivated by p53.Science advances · 2017Article
- Genetic Manipulation of Leishmania donovani to Explore the Involvement of Argininosuccinate Synthase in Oxidative Stress Management.PLoS neglected tropical diseases · 2016Article
- Isolation and characterization of Bradykinin potentiating peptides from Agkistrodon bilineatus venom.Proteome science · 2016Article
- Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-de pend ent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, alpha-methyl-dl-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases.
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