ArticleAmerican journal of physiology. Renal physiology2008
The reactive nitrogen species peroxynitrite is a potent inhibitor of renal Na-K-ATPase activity.
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Maternal Infection Induces Neuronal Structure and Behavioural Alterations in Experimental Meningitis Rat Model.Developmental neuroscience · 2026Article
- Oxidative Stress in the Regulation of Autosis-Related Proteins.Antioxidants (Basel, Switzerland) · 2025Review
- Molecular Basis of Na, K-ATPase Regulation of Diseases: Hormone and FXYD2 Interactions.International journal of molecular sciences · 2024Review
- Interplay between the Redox System and Renal Tubular Transport.Antioxidants (Basel, Switzerland) · 2024Review
- Natural Polyphenols May Normalize Hypochlorous Acid-Evoked Hemostatic Abnormalities in Human Blood.Antioxidants (Basel, Switzerland) · 2022Article
- Cationic amino acid transporters and their modulation by nitric oxide in cardiac muscle cells.Biophysical reviews · 2021Review
- The Effect of Curcumin Nanoparticles on Cisplatin-Induced Cardiotoxicity in Male Wistar Albino Rats.Cardiovascular toxicology · 2021Article
- The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.International journal of molecular sciences · 2020Review
- Peroxynitrite and 4-Hydroxynonenal Inactivate Breast Cancer Resistance Protein/ABCG2.BioMed research international · 2019Article
- Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- Article
- Threshold levels of extracellular l-arginine that trigger NOS-mediated ROS/RNS production in cardiac ventricular myocytes.American journal of physiology. Cell physiology · 2017Article
- Enhancement in cellular Na+K+ATPase activity by low doses of peroxynitrite in mouse renal tissue and in cultured HK2 cells.Physiological reports · 2016Article
- Carbonylation Modification Regulates Na/K-ATPase Signaling and Salt Sensitivity: A Review and a Hypothesis.Frontiers in physiology · 2016Review
- The Influence of Na(+), K(+)-ATPase on Glutamate Signaling in Neurodegenerative Diseases and Senescence.Frontiers in physiology · 2016Review
- Changes in the Distribution of the α 3 Na(+)/K(+) ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during Development.International journal of cell biology · 2014Article
- Nitric oxide regulates cardiac intracellular Na⁺ and Ca²⁺ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.Journal of molecular and cellular cardiology · 2013Article
- Mechanisms associated to impaired activity of cardiac P-type ATPases in endothelial nitric oxide synthase knockout mice.Journal of physiology and biochemistry · 2013Article
- 3-Methylcrotonylglycine disrupts mitochondrial energy homeostasis and inhibits synaptic Na(+),K (+)-ATPase activity in brain of young rats.Cellular and molecular neurobiology · 2012Article
- Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling.International journal of nephrology · 2012Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Peroxynitrite is a reactive nitrogen species produced when nitric oxide and superoxide react. In vivo studies suggest that reactive oxygen species and, perhaps, peroxynitrite can influence Na-K-ATPase function. However, the direct effects of peroxynitrite on Na-K-ATPase function remain unknown. We show that a single bolus addition of peroxynitrite inhibited purified renal Na-K-ATPase activity, with IC50 of 107+/-9 microM. To mimic cellular/physiological production of peroxynitrite, a syringe pump was used to slowly release (approximately 0.85 microM/s) peroxynitrite. The inhibition of Na-K-ATPase activity induced by this treatment was similar to that induced by a single bolus addition of equal cumulative concentration. Peroxynitrite produced 3-nitrotyrosine residues on the alpha, beta, and FXYD subunits of the Na pump. Interestingly, the flavonoid epicatechin, which prevented tyrosine nitration, was unable to blunt peroxynitrite-induced ATPase inhibition, suggesting that tyrosine nitration is not required for inhibition. Peroxynitrite led to a decrease in iodoacetamidofluorescein labeling, implying that cysteine modifications were induced. Glutathione was unable to reverse ATPase inhibition. The presence of Na+ and low MgATP during peroxynitrite treatment increased the IC50 to 145+/-10 microM, while the presence of K+ and low MgATP increased the IC50 to 255+/-13 microM. This result suggests that the EPNa conformation of the pump is slightly more sensitive to peroxynitrite than the E(K) conformation. Taken together, these results show that peroxynitrite is a potent inhibitor of Na-K-ATPase activity and that peroxynitrite can induce amino acid modifications to the pump.
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