Cited by 692Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols

Open access

Kuzkaya, Nermin, Weissmann, Norbert, Harrison, David G., Dikalov, Sergey·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m302227200

Open this paper in CoChat — free account Open PDF

Abstract

Tetrahydrobiopterin (BH4) serves as a critical co-factor for the endothelial nitric-oxide synthase (eNOS). A deficiency of BH4 results in eNOS uncoupling, which is associated with increased superoxide and decreased NO* production. BH4 has been suggested to be a target for oxidation by peroxynitrite (ONOO-), and ascorbate has been shown to preserve BH4 levels and enhance endothelial NO* production; however, the mechanisms underlying these processes remain poorly defined. To gain further insight into these interactions, the reaction of ONOO- with BH4 was studied using electron spin resonance and the spin probe 1-hydroxy-3-carboxy-2,2,5-tetramethyl-pyrrolidine. ONOO- reacted with BH4 6-10 times faster than with ascorbate or thiols. The immediate product of the reaction between ONOO- and BH4 was the trihydrobiopterin radical (BH3.), which was reduced back to BH4 by ascorbate, whereas thiols were not efficient in recycling of BH4. Uncoupling of eNOS caused by peroxynitrite was investigated in cultured bovine aortic endothelial cells (BAECs) by measuring superoxide and NO* using spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine and the NO*-spin trap iron-diethyldithiocarbamate. Bolus ONOO-, the ONOO- donor 3-morpholinosydnonimine, and an inhibitor of BH4 synthesis (2,4-diamino-6-hydroxypyrimidine) uncoupled eNOS, increasing superoxide and decreasing NO* production. Exogenous BH4 supplementation restored endothelial NO* production. Treatment of BAECs with both BH4 and ascorbate prior to ONOO- prevented uncoupling of eNOS by ONOO-. This study demonstrates that endothelial BH4 is a crucial target for oxidation by ONOO- and that the BH4 reaction rate constant exceeds those of thiols or ascorbate. We confirmed that ONOO- uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles BH3. radical back to BH4.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.m302227200

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Nitric oxide synthases: structure, function and inhibition
ALDERTON, W. K., COOPER, C. E., & KNOWLES, R. G. (2001) · Biochemical Journal · doi:10.1042/bj3570593 · Cited by 4,110
Peroxynitrite oxidation of sulfhydryls.
Radí, R., Beckman, J. S., Bush, K., & Freeman, B. Α. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64313-7 · Cited by 2,492
Regulation of biosynthesis of nitric oxide.
Nathan, C., & Xie, Q. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36703-0 · Cited by 1,669
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Landmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Self-citation
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Landmesser, U., Dikalov, S., Price, S. R., McCann, L. A., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci14172 · Cited by 1,652
Self-citation
Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors
Vásquez-Vivar, J., Kalyanaraman, B., Martásek, P., Hogg, N., Masters, B. S. S., Karoui, H., Tordo, P., & Pritchard, K. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9220 · Cited by 1,484
Nitric oxide synthase structure and mechanism
Marletta, M. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31375-9 · Cited by 1,338
Mammalian nitric oxide synthases
Stuehr, D. J. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00016-x · Cited by 996
Simulation of Multiple Isotropic Spin-Trap EPR Spectra
Duling, D. (1994) · Journal of Magnetic Resonance Series B · doi:10.1006/jmrb.1994.1062 · Cited by 940
Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.
Ting, H. H., Timimi, F. K., Boles, K., Creager, S. J., Ganz, P., & Creager, M. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118394 · Cited by 869

Flagged first, then by citations

Show all 50 references

Research works printed but not linked: 3

Gorren, 1998, Biochemistry (Mosc.), 63, 734
Dikalov, 1998, J. Pharmacol. Exp. Ther., 286, 938
Fink, 2002, Free Radic. Biol. Med., 33, 366

Sorted by citations

Items 201–300 of 691

Free radical production by dysfunctional eNOS
Verhaar, M. C. (2004) · Heart · doi:10.1136/hrt.2003.029405 · Cited by 90
The Two Faces of Endothelial Nitric Oxide Synthase in the Pathophysiology of Atherosclerosis
Kawashima, S. (2004) · Endothelium · doi:10.1080/10623320490482637 · Cited by 89
pH-sensitive Eudragit® L 100 nanoparticles promote cutaneous penetration and drug release on the skin
Dong, P., Sahle, F. F., Lohan, S. B., Saeidpour, S., Albrecht, S., Teutloff, C., Bodmeier, R. A., Unbehauen, M. L., Wolff, C., Haag, R., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.12.045 · Cited by 88
Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor
Eichwald, T., da Silva, L. D. B., Pires, A. S., Niero, L., Schnorrenberger, E., Filho, C. C., Espíndola, G., Huang, W., Guillemin, G. J., Abdenur, J. E., et al. (2023) · Antioxidants · doi:10.3390/antiox12051037 · Cited by 87
Endothelial mechanisms of endothelial dysfunction in patients with obstructive sleep apnea
Feng, J., Zhang, D., & Chen, B.-Y. (2011) · Sleep And Breathing · doi:10.1007/s11325-011-0519-8 · Cited by 89
Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin
Holowatz, L. A., Thompson, C. S., & Kenney, W. L. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00648.2006 · Cited by 88
Antioxidant therapy in critical care—Is the microcirculation the primary target?
Biesalski, H. K., & McGregor, G. P. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000278598.95294.c5 · Cited by 86
Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction
Wood, K. C., Hebbel, R. P., Lefer, D. J., & Granger, D. N. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.12.015 · Cited by 87
Apocynin but Not Allopurinol Prevents and Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat
Zhang, Y., Chan, M. M. K., Andrews, M. C., Mori, T. A., Croft, K. D., McKenzie, K. U. S., Schyvens, C. G., & WHITWORTH, J. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.02.017 · Cited by 87
Oxidized low density lipoprotein, stem cells, and atherosclerosis
Yang, H., Mohamed, A. S. S., & Zhou, S. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-85 · Cited by 84
Therapeutic Potential of Tetrahydrobiopterin for Treating Vascular and Cardiac Disease
Moens, A. L., & Kass, D. A. (2007) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318123f854 · Cited by 83
Arginase inhibition alleviates hypertension associated with diabetes: Effect on endothelial dependent relaxation and NO production
El‐Bassossy, H. M., El‐Fawal, R., & Fahmy, A. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.01.001 · Cited by 83
Endothelial dysfunction in rat adjuvant‐induced arthritis: Vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase
Haruna, Y., Morita, Y., Komai, N., Yada, T., Sakuta, T., Tomita, N., Fox, D. A., & Kashihara, N. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21891 · Cited by 83
Vascular Dysfunction and Chronic Obstructive Pulmonary Disease
Ives, S. J., Harris, R. A., Witman, M. A., Fjeldstad, A. S., Garten, R. S., McDaniel, J., Wray, D. W., & Richardson, R. S. (2013) · Hypertension · doi:10.1161/hypertensionaha.113.02255 · Cited by 82
Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells
May, J. M., Qu, Z., & Meredith, M. E. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.08.054 · Cited by 86
Selective Recapitulation of Conserved and Nonconserved Regions of Putative NOXA1 Protein Activation Domain Confers Isoform-specific Inhibition of Nox1 Oxidase and Attenuation of Endothelial Cell Migration
Ranayhossaini, D., Rodriguez, A. I., Sahoo, S., Chen, B. B., Mallampalli, R. K., Kelley, E. E., Csányi, G., Gladwin, M. T., Romero, G. G., & Pagano, P. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.521344 · Cited by 83
Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies
Mortensen, A., & Lykkesfeldt, J. (2014) · Nitric Oxide · doi:10.1016/j.niox.2013.12.001 · Cited by 80
Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia
Mészáros, M., & Bikov, A. (2022) · Biomedicines · doi:10.3390/biomedicines10112754 · Cited by 83
Smoking cessation and vascular endothelial function
Higashi, Y. (2023) · Hypertension Research · doi:10.1038/s41440-023-01455-z · Cited by 84
Nitric Oxide Synthase Stabilizes the Tetrahydrobiopterin Cofactor Radical by Controlling Its Protonation State
Stoll, S., NejatyJahromy, Y., Woodward, J. J., Ozarowski, A., Marletta, M. A., & Britt, R. D. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105372s · Cited by 84
Current concepts on the pathophysiology of portal hypertension
Rodrı́guez-Vilarrupla, A., Fernández, M., Bosch, J., & García‐Pagán, J. C. (2007) · Annals of Hepatology · doi:10.1016/s1665-2681(19)31950-7 · Cited by 80
GCH1 Haplotype Determines Vascular and Plasma Biopterin Availability in Coronary Artery Disease
Antoniades, C. A., Shirodaria, C. C., Assche, T. V., Cunnington, C., Tegeder, I., Lötsch, J., Guzik, T. J., Leeson, P., Diesch, J., Tousoulis, D., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.12.062 · Cited by 79
Antihypertensive Role of Polyphenols
Rodrigo, R., Gil, D., Miranda-Merchak, A., & Kalantzidis, G. (2012) · Advances in clinical chemistry · doi:10.1016/b978-0-12-394383-5.00014-x · Cited by 78
Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris
Jarocka-Karpowicz, I., Biernacki, M., Wroński, A., Gęgotek, A., & Skrzydlewska, E. (2020) · Biomolecules · doi:10.3390/biom10030367 · Cited by 78
Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification
Liu, Z., Dong, N., Hui, H., Wang, Y., Liu, F., Xu, L., Liu, M., Rao, Z., Yuan, Z., Shang, Y., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac037 · Cited by 78
Review: The role of the L-arginine-nitric oxide pathway in preeclampsia
López-Jaramillo, P. A., Arenas, W. D., Garcia, R. G., Rincón, M. Y., & López, M. (2008) · Therapeutic Advances in Cardiovascular Disease · doi:10.1177/1753944708092277 · Cited by 79
Type 2 Diabetes Restricts Multipotency of Mesenchymal Stem Cells and Impairs Their Capacity to Augment Postischemic Neovascularization in db/db Mice
Yan, J., Tie, G., Wang, S., Messina, K. E., Didato, S., Guo, S., & Messina, L. M. (2012) · Journal of the American Heart Association · doi:10.1161/jaha.112.002238 · Cited by 78
Site and mechanism of uncoupling of nitric-oxide synthase: Uncoupling by monomerization and other misconceptions
Gebhart, V., Reiß, K., Kollau, A., Mayer, B., & Gorren, A. C. F. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.04.007 · Cited by 80
Hydrogen Peroxide Promotes Endothelial Dysfunction by Stimulating Multiple Sources of Superoxide Anion Radical Production and Decreasing Nitric Oxide Bioavailability
Witting, P. K., Rayner, B. S., Wu, B. J., Ellis, N. A., & Stocker, R. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000107512 · Cited by 77
Intravenous Ascorbic Acid Infusion Improves Myocardial Perfusion Grade During Elective Percutaneous Coronary Intervention
Basili, S., Tanzilli, G., Mangieri, E., Raparelli, V., Santo, S. D., Pignatelli, P., & Violi, F. (2010) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2009.10.025 · Cited by 77
Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide
Atalay, S., Dobrzyńska, I., Gęgotek, A., & Skrzydlewska, E. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101613 · Cited by 76
The Role of Oxidative Stress in Acute Ischemic Stroke‐Related Thrombosis
Li, Z., Bi, R., Sun, S., Chen, S., Chen, J., Hu, B., & Jin, H. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/8418820 · Cited by 76
Function of NADPH Oxidase 1 in Pulmonary Arterial Smooth Muscle Cells After Monocrotaline-Induced Pulmonary Vascular Remodeling
Veit, F., Pak, O., Egemnazarov, B., Roth, M., Kosanovic, D., Seimetz, M., Sommer, N., Ghofrani, H. A., Seeger, W., Grimminger, F., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4904 · Cited by 76
Oxidative stress contributes to large elastic arterial stiffening across the stages of the menopausal transition
Hildreth, K. L., Kohrt, W. M., & Moreau, K. L. (2013) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000116 · Cited by 76
eNOS Gene Therapy Exacerbates Hepatic Ischemia-Reperfusion Injury in Diabetes
Elrod, J. W., Duranski, M. R., Langston, W., Greer, J. J. M., Tao, L., Dugas, T. R., Kevil, C. G., Champion, H. C., & Lefer, D. J. (2006) · Circulation Research · doi:10.1161/01.res.0000231306.03510.77 · Cited by 75
Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective
Santilli, F., Davı̀, G., & Patrono, C. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.06.009 · Cited by 78
The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation
Gęgotek, A., Biernacki, M., Ambrożewicz, E., Surażyński, A., Wroński, A., & Skrzydlewska, E. (2015) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2015.11.005 · Cited by 74
Mechanisms of H2O2-Induced Oxidative Stress in Endothelial Cells Exposed to Physiologic Shear Stress
Coyle, C. H., & Kader, K. N. (2007) · ASAIO Journal · doi:10.1097/01.mat.0000247157.84350.e8 · Cited by 72
Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: Implication of NADPH oxidase
Rouhanizadeh, M., Hwang, J., Clempus, R. E., Marcu, L., Lassegue, B. P., Sevanian, A., & Hsiai, T. K. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.07.013 · Cited by 73
A novel role for small molecule glycomimetics in the protection against lipid-induced endothelial dysfunction: Involvement of Akt/eNOS and Nrf2/ARE signaling
Mahmoud, A. M., Wilkinson, F. L., Jones, A. M., Wilkinson, J. A., Romero, M., Duarte, J., & Alexander, M. Y. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.08.013 · Cited by 72
Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice
Ow, C. P. C., Trask-Marino, A. L., Betrie, A. H., Evans, R. G., May, C. N., & Lankadeva, Y. R. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173798 · Cited by 75
Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?
Álvarez, M. C., Caldiz, C. I., Fantinelli, J. C., Garciarena, C. D., Cónsole, G. M., de Cingolani, G. E. C., & Mosca, S. M. (2008) · Hypertension Research · doi:10.1291/hypres.31.1465 · Cited by 71
Diabetes, obesity, and erectile dysfunction
Tamler, R. (2009) · Gender Medicine · doi:10.1016/j.genm.2008.12.003 · Cited by 73
Targeted Detoxification of Selected Reactive Oxygen Species in the Vascular Endothelium
Shuvaev, V. V., Christofidou‐Solomidou, M., Bhora, F. Y., Laude, K. M., Cai, H. “., Dikalov, S., Arguiri, E., Solomides, C., Albelda, S. Μ., Harrison, D. G., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.156877 · Cited by 71
Self-citation
Pentaerythritol Tetranitrate Improves Angiotensin II–Induced Vascular Dysfunction via Induction of Heme Oxygenase-1
Schuhmacher, S., Wenzel, P., Schulz, E., Oelze, M. W., Mang, C. F., Kamuf, J., Gori, T., Jansen, T., Knorr, M., Karbach, S. H., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.149542 · Cited by 70
Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations
Neri, M., Riezzo, I., Pomara, C., Schiavone, S., & Turillazzi, E. (2016) · Mediators of Inflammation · doi:10.1155/2016/3423450 · Cited by 71
Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms
Gostner, J. M., Becker, K., Kurz, K., & Fuchs, D. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00097 · Cited by 68
Mechanisms of Increased Vascular Superoxide Production in an Experimental Model of Idiopathic Dilated Cardiomyopathy
Mollnau, H., Oelze, M. W., August, M., Wendt, M., Daiber, A., Schulz, E., Baldus, S. E., Kleschyov, A. L., Materne, A., Wenzel, P., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000190673.41925.9b · Cited by 68
Time-dependent effect of rutin on skin fibroblasts membrane disruption following UV radiation
Gęgotek, A., Bielawska, K., Biernacki, M., Dobrzyńska, I., & Skrzydlewska, E. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.014 · Cited by 69
The Effect of Sea Buckthorn (Hippophae rhamnoides L.) Seed Oil on UV-Induced Changes in Lipid Metabolism of Human Skin Cells
Gęgotek, A., Jastrząb, A., Jarocka-Karpowicz, I., Muszyńska, M., & Skrzydlewska, E. (2018) · Antioxidants · doi:10.3390/antiox7090110 · Cited by 75
Three Different Oxygen-induced Radical Species in Endothelial Nitric-oxide Synthase Oxygenase Domain under Regulation by L-Arginine and Tetrahydrobiopterin
Berka, V., Wu, G., Yeh, H.-C., Palmer, G., & Tsai, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404044200 · Cited by 69
The inhibitory effect of S‐nitrosoglutathione on blood–brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke
Khan, M., Dhammu, T. S., Sakakima, H., Shunmugavel, A., Gilg, A. G., Singh, A. K., & Singh, I. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07947.x · Cited by 68
Production of extracellular superoxide by human lymphoblast cell lines: Comparison of electron spin resonance techniques and cytochrome C reduction assay
Dikalov, S., Li, W., Mehranpour, P., Wang, S. S., & Zafari, A. M. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.12.012 · Cited by 69
Self-citation
Free radicals and antioxidants at a glance using EPR spectroscopy
Spasojević, I. (2011) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2011.591772 · Cited by 69
Nitrotyrosine as a marker for peroxynitrite‐induced neurotoxicity: the beginning or the end of the end of dopamine neurons?
Kuhn, D. M., Sakowski, S. A., Sadidi, M., & Geddes, T. J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02346.x · Cited by 66
Reactive oxygen species (ROS) from NADPH and xanthine oxidase modulate the cutaneous local heating response in healthy humans
Medow, M. S., Bamji, N., Clarke, D. A., Ocon, A. J., & Stewart, J. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01448.2010 · Cited by 63
Melatonin and Nitric Oxide: Two Required Antagonists for Mitochondrial Homeostasis
Acuña-Castroviejo, D., Escames, G., López, L. C., Hitos, A. B., & León, J. (2005) · Endocrine · doi:10.1385/endo:27:2:159 · Cited by 65
Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO– cycle
Pall, M. L. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2007.01.070 · Cited by 65
Stressor-induced NMDAR dysfunction as a unifying hypothesis for the aetiology, pathogenesis and comorbidity of clinical depression
Marsden, W. N. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.06.021 · Cited by 64
The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression
Rabender, C. S., Alam, A., Sundaresan, G., Cardnell, R. J., Yakovlev, V. A., Mukhopadhyay, N. D., Graves, P. R., Zweit, J., & Mikkelsen, R. B. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0057-t · Cited by 63
Chronic NOS inhibition prevents adverse lung remodeling and pulmonary arterial hypertension in caveolin-1 knockout mice
Wunderlich, C., Schmeißer, A., Heerwagen, C., Ebner, B., Schober, K., Braun-Dullaeus, R. C., Schwencke, C., Kasper, M. E., Morawietz, H., & Strasser, R. H. (2008) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2007.11.005 · Cited by 61
Malfunction of Vascular Control in Lifestyle-Related Diseases: Endothelial Nitric Oxide (NO) Synthase/NO System in Atherosclerosis
Kawashima, S. (2004) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fmj04006x6 · Cited by 62
Nitric oxide down‐regulates the expression of the catalytic NADPH oxidase subunit Nox1 in rat renal mesangial cells
Plešková, M., Beck, K., Behrens, M. H., Huwiler, A., Fichtlscherer, B., Wingerter, O., Brandes, R. P., Mülsch, A., & Pfeilschifter, J. M. (2005) · The FASEB Journal · doi:10.1096/fj.05-3791fje · Cited by 61
Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration
Biernacki, M., Ambrożewicz, E., Gęgotek, A., Toczek, M., Bielawska, K., & Skrzydlewska, E. (2017) · Redox Biology · doi:10.1016/j.redox.2017.11.022 · Cited by 60
Loss of nitric oxide and endothelial-derived hyperpolarizing factor-mediated responses in aging
Long, D. A., Newaz, M., Prabhakar, S. S., Price, K. L., Truong, L. D., Feng, L., Mu, W., Oyekan, A., & Johnson, R. J. (2005) · Kidney International · doi:10.1111/j.1523-1755.2005.00671.x · Cited by 60
Antioxidant Vitamin C Prevents Decline in Endothelial Function during Sitting
Wallace, J. P. (2015) · Medical Science Monitor · doi:10.12659/msm.893192 · Cited by 60
Endothelial nitric oxide synthase uncoupling: A novel pathway in OSA induced vascular endothelial dysfunction
Varadharaj, S., Porter, K. M., Pleister, A. P., Wannemacher, J., Sow, A., Jarjoura, D. G., Zweier, J. L., & Khayat, R. (2014) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2014.12.012 · Cited by 65
Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction
Maki-Petaja, K. M., Cheriyan, J., Booth, A. D., Hall, F. C., Brown, J., Wallace, S. M. L., Ashby, M. J., McEniery, C. M., & Wilkinson, I. B. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.02.011 · Cited by 60
Reactive oxygen species: friend or foe?
Sharma, A. K., Taneja, G., Khanna, D., & Rajput, S. K. (2015) · RSC Advances · doi:10.1039/c5ra07927f · Cited by 59
Endothelial Dysfunction and Enhanced Contractility in Microvessels From Ovariectomized Rats
Wang, D., Wang, C., Wu, X., Zheng, W., Sandberg, K. L., Ji, H., Welch, W. J., & Wilcox, C. S. (2014) · Hypertension · doi:10.1161/hypertensionaha.113.02284 · Cited by 59
PPAR-γ agonist, pioglitazone, reduced oxidative and endoplasmic reticulum stress associated with L-NAME-induced hypertension in rats
Soliman, E., Behairy, S., El‐Maraghy, N. N., & Elshazly, S. M. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117047 · Cited by 59
Regulation of Vascular Function and Inflammation via Cross Talk of Reactive Oxygen and Nitrogen Species from Mitochondria or NADPH Oxidase—Implications for Diabetes Progression
Daiber, A., Steven, S., Vujačić-Mirski, K., Kalinovic, S., Oelze, M. W., Lisa, F. D., & Münzel, T. F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103405 · Cited by 59
Oxidized Low-Density Lipoprotein Induces Apoptosis in Endothelial Progenitor Cells by Inactivating the Phosphoinositide 3-Kinase/Akt Pathway
Tie, G., Yan, J., Yang, Y., Park, B. D., Messina, J. A., Raffaï, R. L., Nowicki, P. T., & Messina, L. M. (2010) · Journal of Vascular Research · doi:10.1159/000313879 · Cited by 59
Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management
Janković, A., Korać, A., Buzadžić, B., Stančić, A., Otašević, V., Ferdinándy, P., Daiber, A., & Korać, B. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13498 · Cited by 60
S-Nitrosylation in Tumor Microenvironment
Sharma, V., Fernando, V., Letson, J., Walia, Y., Zheng, X., Fackelman, D., & Furuta, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094600 · Cited by 59
Antioxidant and pro-oxidant mechanisms of (+) catechin in microsomal CYP2E1-dependent oxidative stress
Caro, A. A., Davis, A., Fobare, S., Horan, N., Ryan, C., & Schwab, C. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.09.001 · Cited by 57
Blockade of NADPH Oxidase Restores Vasoreparative Function in Diabetic CD34 + Cells
Jarajapu, Y. P. R., Caballero, S., Verma, A., Nakagawa, T., Lo, M. C., Li, Q., & Grant, M. B. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-70911 · Cited by 56
Improvement in endothelial function in cardiovascular disease - Is arginase the target?
Mahdi, A., Kövamees, O., & Pernow, J. (2019) · International Journal of Cardiology · doi:10.1016/j.ijcard.2019.11.004 · Cited by 59
Simultaneous Determination of Superoxide and Hydrogen Peroxide in Macrophage RAW 264.7 Cell Extracts by Microchip Electrophoresis with Laser-Induced Fluorescence Detection
Li, H., Li, Q., Wang, X., Xu, K., Chen, Z., Gong, X., Liu, X., Tong, L., & Tang, B. (2009) · Analytical Chemistry · doi:10.1021/ac801777c · Cited by 55
Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide
Gęgotek, A., Bielawska, K., Biernacki, M., Zaręba, I., Surażyński, A., & Skrzydlewska, E. (2017) · Archives of Dermatological Research · doi:10.1007/s00403-017-1729-0 · Cited by 55
MicroRNAs Regulating Reactive Oxygen Species in Cardiovascular Diseases
Gong, Y.-Y., Luo, J., Wang, L., & Huang, Y. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7328 · Cited by 55
A novel role for endothelial tetrahydrobiopterin in mitochondrial redox balance
Bailey, J. D., Shaw, A., Fischer, R., Ryan, B. J., Kessler, B. M., McCullagh, J., Wade‐Martins, R., Channon, K. M., & Crabtree, M. J. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.012 · Cited by 53
The Role of Natural Antioxidants in the Prevention of Dementia—Where Do We Stand and Future Perspectives
Jurcău, A. (2021) · Nutrients · doi:10.3390/nu13020282 · Cited by 54
Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats
Lam, K.-K., Lee, Y., Hsiao, G., Chen, S.-Y., & Yen, M. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000182806.99137.5e · Cited by 53
Early determinants of H2O2-induced endothelial dysfunction
Boulden, B. M., Widder, J. D., Allen, J. C., Smith, D. A., Al-Baldawi, R. N., Harrison, D. G., Dikalov, S., Jo, H., & Dudley, S. C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.030 · Cited by 53
Self-citation
High Vitamin C Status Is Associated with Elevated Mood in Male Tertiary Students
Pullar, J., Carr, A., Bozonet, S., & Vissers, M. (2018) · Antioxidants · doi:10.3390/antiox7070091 · Cited by 52
Administration of tetrahydrobiopterin improves the microcirculation and outcome in an ovine model of septic shock*
He, X., Su, F., Velissaris, D., Salgado, D. R., Barros, D. D. S., Lorent, S., Taccone, F. S., Vincent, J., & Backer, D. D. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e31825b88ba · Cited by 52
Does Vitamin C Deficiency Increase Lifestyle-Associated Vascular Disease Progression? Evidence Based on Experimental and Clinical Studies
Tveden‐Nyborg, P., & Lykkesfeldt, J. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5382 · Cited by 52
Cardiovascular and Metabolic Effects of Açaí, an Amazon Plant
de Moura, R. S., & Resende, Â. C. (2015) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000347 · Cited by 52
Pathophysiology of reactive oxygen species (ROS)
de la Lastra, J. M. P., Andrés, C. M. C., Munguira, E. B., Juan, C. A., & Pérez‐Lebeña, E. (2026) · Archives of Toxicology · doi:10.1007/s00204-025-04276-w · Cited by 61
The therapeutic potential of diet on immune-related diseases: based on the regulation on tryptophan metabolism
Lin, J., Sun‐Waterhouse, D., & Cui, C. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1934813 · Cited by 49
Antidiabetic Agents and Endothelial Dysfunction – Beyond Glucose Control
Eriksson, L., & Nyström, T. (2015) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12402 · Cited by 49
Vascular Dysfunction in Streptozotocin-Induced Experimental Diabetes Strictly Depends on Insulin Deficiency
Oelze, M. W., Knorr, M., Schuhmacher, S., Heeren, T. F. C., Otto, C., Schulz, E., Reifenberg, K., Wenzel, P., Münzel, T. F., & Daiber, A. (2011) · Journal of Vascular Research · doi:10.1159/000320627 · Cited by 48
Antioxidants and endothelial nitric oxide synthesis
Heller, R., Werner‐Felmayer, G., & Werner, E. R. (2005) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-005-0009-7 · Cited by 48
Native C-reactive protein induces endothelial dysfunction in ApoE−/− mice: Implications for iNOS and reactive oxygen species
Schwedler, S. B., Kuhlencordt, P. J., Ponnuswamy, P., Hatiboglu, G., Quaschning, T., Widder, J. D., Wanner, C., Potempa, L. A., & Galle, J. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.06.013 · Cited by 48
Dose dependent effects of reactive oxygen and nitrogen species on the function of neuronal nitric oxide synthase
Sun, J., Druhan, L. J., & Zweier, J. L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.01.003 · Cited by 47
Cytoprotective and antioxidant effects of human lactoferrin against H 2 O 2 -induced oxidative stress in human umbilical vein endothelial cells
Safaeian, L., Javanmard, S. H., Mollanoori, Y., & Dana, N. (2015) · Advanced Biomedical Research · doi:10.4103/2277-9175.164010 · Cited by 47
Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes
Ceriello, A., Piconi, L., Esposito, K., & Giugliano, D. (2007) · Diabetes Care · doi:10.2337/dc07-0318 · Cited by 47
Diosmetin Ameliorates Vascular Dysfunction and Remodeling by Modulation of Nrf2/HO-1 and p-JNK/p-NF-κB Expression in Hypertensive Rats
Meephat, S., Prasatthong, P., Potue, P., Bunbupha, S., Pakdeechote, P., & Maneesai, P. (2021) · Antioxidants · doi:10.3390/antiox10091487 · Cited by 49
Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice
Mahmood, Q., Wang, G., Wu, G., Wang, H., Zhou, C., Yang, H., Liu, Z., Han, F., & Zhao, K. (2016) · Phytomedicine · doi:10.1016/j.phymed.2016.12.004 · Cited by 46

Authors: Kuzkaya, N., Weissmann, N., Harrison, D. G., & Dikalov, S.
Affiliations: Emory University (US)
Justus-Liebig-Universität Gießen (DE)
Corresponding author: Dikalov, Sergey
ORCID: Weissmann, Norbert
Harrison, David G.
Dikalov, Sergey
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-06
Volume: 278
Issue: 25
Pages: 22546-22554
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m302227200
OpenAlex: W2058242086
Cited by: 692
References: 50
Citations by year: 2026: 18 · 2025: 15 · 2024: 17 · 2023: 20 · 2022: 23 · 2021: 29 · 2020: 22 · 2019: 24 · 2018: 31 · 2017: 23 · 2016: 24 · 2015: 33 · 2014: 33 · 2013: 25 · 2012: 44
FWCI: 20.60
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6324 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (SFB-547)
National Institutes of Health (HL058000, PO-1 HL058000)
National Heart, Lung, and Blood Institute (R01HL039006, P0-1 HL058000-06, P01HL058000)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: peroxynitrite, tetrahydrobiopterin, vitamin C, thiols, endothelial nitric oxide synthase, eNOS uncoupling, superoxide, nitric oxide, SIN-1, 2,4-diamino-6-hydroxypyrimidine, endothelial cells
MeSH terms: Animals, Aorta, Ascorbic Acid, Biopterins, Cattle, Cells, Cultured, Endothelium, Vascular, Kinetics, Spin Labels, Sulfhydryl Compounds, Nitric Oxide Synthase, Nitric Oxide Donors, Peroxynitrous Acid, Nitric Oxide Synthase Type III

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks