GKT137831 and Hydrogen Peroxide Increase the Release of 6-nitrodopamine from the Human Umbilical Artery, Rat-isolated Right Atrium, and Rat-isolated Vas Deferens

Overview

Journal Front Pharmacol

Date 2024 Apr 22

PMID 38645555

Authors

Jose Britto-Junior

Rafael Furlaneto

Antonio Tiago Lima

Mariana Goncalves de Oliveira

Beatrice Severino

Francesco Frecentese

Ferdinando Fiorino

Giuseppe Caliendo

Marcelo Nicolas Muscara

Gilberto De Nucci

Affiliations

Soon will be listed here.

Abstract

The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with N-nitro-L-arginine methyl ester (L-NAME). In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Pre-incubation (30 min) of the tissues with GKT137831 (1 μM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 μM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (HO) (100 μM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 μM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 μM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and HO. The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution.

References

Bartesaghi S, Radi R . Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration. Redox Biol. 2017; 14:618-625. PMC: 5694970. DOI: 10.1016/j.redox.2017.09.009. View

Takac I, Schroder K, Zhang L, Lardy B, Anilkumar N, Lambeth J . The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem. 2011; 286(15):13304-13. PMC: 3075677. DOI: 10.1074/jbc.M110.192138. View

Vlahos C, Matter W, Hui K, Brown R . A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 1994; 269(7):5241-8. View

Britto-Junior J, Campos R, Peixoto M, Lima A, Jacintho F, Monica F . 6-Nitrodopamine is an endogenous selective dopamine receptor antagonist in Chelonoidis carbonaria aorta. Comp Biochem Physiol C Toxicol Pharmacol. 2022; 260:109403. DOI: 10.1016/j.cbpc.2022.109403. View

Zatz R, De Nucci G . Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System. Physiology (Bethesda). 2023; 39(1):44-59. PMC: 11283902. DOI: 10.1152/physiol.00020.2023. View

Shintani F, Kinoshita T, Kanba S, Ishikawa T, Suzuki E, Sasakawa N . Bioactive 6-nitronorepinephrine identified in mammalian brain. J Biol Chem. 1996; 271(23):13561-5. DOI: 10.1074/jbc.271.23.13561. View

Lima A, Santos E, Britto-Junior J, de Souza V, Schenka A, Campos R . Release of 6-nitrodopamine modulates vascular reactivity of Pantherophis guttatus aortic rings. Comp Biochem Physiol C Toxicol Pharmacol. 2022; 262:109471. DOI: 10.1016/j.cbpc.2022.109471. View

Aoyama T, Paik Y, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L . Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012; 56(6):2316-27. PMC: 3493679. DOI: 10.1002/hep.25938. View

Becker B, Reinholz N, Leipert B, Raschke P, Permanetter B, Gerlach E . Role of uric acid as an endogenous radical scavenger and antioxidant. Chest. 1991; 100(3 Suppl):176S-181S. DOI: 10.1378/chest.100.3_supplement.176s. View

10.

Sies H, Jones D . Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7):363-383. DOI: 10.1038/s41580-020-0230-3. View

11.

Thomas S, Chen K, Keaney Jr J . Hydrogen peroxide activates endothelial nitric-oxide synthase through coordinated phosphorylation and dephosphorylation via a phosphoinositide 3-kinase-dependent signaling pathway. J Biol Chem. 2001; 277(8):6017-24. DOI: 10.1074/jbc.M109107200. View

12.

Konior A, Schramm A, Czesnikiewicz-Guzik M, Guzik T . NADPH oxidases in vascular pathology. Antioxid Redox Signal. 2013; 20(17):2794-814. PMC: 4026218. DOI: 10.1089/ars.2013.5607. View

13.

Iuga C, Alvarez-Idaboy J, Vivier-Bunge A . ROS initiated oxidation of dopamine under oxidative stress conditions in aqueous and lipidic environments. J Phys Chem B. 2011; 115(42):12234-46. PMC: 3198543. DOI: 10.1021/jp206347u. View

14.

von Lohneysen K, Noack D, Jesaitis A, Dinauer M, Knaus U . Mutational analysis reveals distinct features of the Nox4-p22 phox complex. J Biol Chem. 2008; 283(50):35273-82. PMC: 2596391. DOI: 10.1074/jbc.M804200200. View

15.

Erudaitius D, Huang A, Kazmi S, Buettner G, Rodgers V . Peroxiporin Expression Is an Important Factor for Cancer Cell Susceptibility to Therapeutic H2O2: Implications for Pharmacological Ascorbate Therapy. PLoS One. 2017; 12(1):e0170442. PMC: 5249139. DOI: 10.1371/journal.pone.0170442. View

16.

Britto-Junior J, Pereira do Prado G, Chiavegatto S, Cunha F, Moraes M, Moraes M . The importance of the endothelial nitric oxide synthase on the release of 6-nitrodopamine from mouse isolated atria and ventricles and their role on chronotropism. Nitric Oxide. 2023; 138-139:26-33. DOI: 10.1016/j.niox.2023.06.001. View

17.

Britto-Junior J, Coelho-Silva W, Murari G, Nash C, Monica F, Antunes E . 6-Nitrodopamine is released by human umbilical cord vessels and modulates vascular reactivity. Life Sci. 2021; 276:119425. DOI: 10.1016/j.lfs.2021.119425. View

18.

Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C . Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 2010; 299(6):F1348-58. DOI: 10.1152/ajprenal.00028.2010. View

19.

Shiva S . Nitrite: A Physiological Store of Nitric Oxide and Modulator of Mitochondrial Function. Redox Biol. 2013; 1(1):40-44. PMC: 3661298. DOI: 10.1016/j.redox.2012.11.005. View

20.

Altenhofer S, Radermacher K, Kleikers P, Wingler K, Schmidt H . Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement. Antioxid Redox Signal. 2014; 23(5):406-27. PMC: 4543484. DOI: 10.1089/ars.2013.5814. View