S-glutathionylation uncouples eNOS and regulates its cellular and vascular function
Open accessAbstract
Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(•-)), which are key mediators of cellular signalling. In the presence of Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l-arginine (l-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH(4)) and l-Arg. In the absence of BH(4), NO synthesis is abrogated and instead O(2)(•-) is generated. While NOS dysfunction occurs in diseases with redox stress, BH(4) repletion only partly restores NOS activity and NOS-dependent vasodilation. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation. Under oxidative stress, S-glutathionylation occurs through thiol-disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione. Cysteine residues are critical for the maintenance of eNOS function; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O(2)(•-) generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O(2)(•-) generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol-specific reducing agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS is a pivotal switch providing redox regulation of cellular signalling, endothelial function and vascular tone.
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
Cites
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?
At least three eNOS residues are susceptible to S-glutathionylation: Cys689, Cys908, and Cys382.
“At least three residues have been shown to be susceptible: Cys689, Cys908 (162), and Cys382 (160)”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [162]
eNOS can be modified posttranslationally by S-glutathionylation.
“Recent reports indicate that eNOS can also be modified posttranslationally by S-glutathionylation”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [162]
S-glutathionylation increases eNOS uncoupling and formation of superoxide with diminished NO synthesis activity.
“The reaction increases eNOS uncoupling and the formation of superoxide with diminished NO synthesis activity.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [162]
Addition of l-NAME decreases superoxide production only in part, indicating that most superoxide production occurs in the reductase domain via electron transfer from reduced FAD and FMN to molecular oxygen.
“Consistent with this hypothesis, the addition of the inhibitor l-NAME decreases superoxide production only in part, indicating that most of the superoxide production occurs in the reductase domain via electron transfer from the reduced FAD and FMN to molecular oxygen (162) (Table 6, Figs. 11, 12).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [162]
Glutathionylation of Cys689 and Cys908 causes eNOS uncoupling.
“The glutathionylation of Cys689 and Cys908 causes eNOS uncoupling.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [162]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,745 · see citing works
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,612 · see citing works
Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase
Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C. J., Reed, R. R., & Snyder, S. H. (1991) · Nature · doi:10.1038/351714a0 · Cited by 2,354 · see citing works
Hydrogen sulphide and its therapeutic potential
Szabó, C. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2425 · Cited by 2,039 · see citing works
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 · see citing works
Acylation Targets Endothelial Nitric-oxide Synthase to Plasmalemmal Caveolae
Shaul, P. W., Smart, E. J., Robinson, L. J., German, Z., Yuhanna, I. S., Ying, Y., Anderson, R. G. W., & Michel, T. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.11.6518 · Cited by 800 · see citing works
Xia, Y., Dawson, V. L., Dawson, T. M., Snyder, S. H., & Zweier, J. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6770 · Cited by 718 · see citing works
Self-citationSuperoxide Generation from Endothelial Nitric-oxide Synthase
Xia, Y., Tsai, A.-L., Berka, V., & Zweier, J. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25804 · Cited by 705 · see citing works
Self-citationRapoport, R. M., Draznin, M. B., & Murad, F. (1983) · Nature · doi:10.1038/306174a0 · Cited by 631 · see citing works
Redox modifications of protein-thiols: emerging roles in cell signaling.
Biswas, S., Chida, A., & Rahman, I. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.044 · Cited by 631 · see citing works
Update on Mechanism and Catalytic Regulation in the NO Synthases
Stuehr, D. J., Santolini, J., Wang, Z., Wei, C., & Adak, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400017200 · Cited by 516 · see citing works
Free radical biology and medicine: it's a gas, man!
Pryor, W. A., Houk, K. N., Foote, C. S., Fukuto, J. M., Ignarro, L. J., Squadrito, G. L., & Davies, K. J. A. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00614.2005 · Cited by 465 · see citing works
Endothelial Nitric-oxide Synthase
Rodríguez‐Crespo, I., Gerber, N. C., & de Montellano, P. R. O. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.19.11462 · Cited by 323 · see citing works
Structural Basis for Isozyme-specific Regulation of Electron Transfer in Nitric-oxide Synthase
Garcin, E. D., Bruns, C. M., Lloyd, S. J., Hosfield, D. J., Tiso, M., Gachhui, R., Stuehr, D. J., Tainer, J. A., & Getzoff, E. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406204200 · Cited by 285 · see citing works
S‐Glutathionylation: from redox regulation of protein functions to human diseases
Giustarini, D., Rossi, R., Milzani, A., Colombo, R., & Dalle‐Donne, I. (2004) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2004.tb00275.x · Cited by 279 · see citing works
On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies
Muscoli, C., Cuzzocrea, S., Riley, D. P., Zweier, J. L., Thiemermann, C., Wang, Z., & Salvemini, D. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705430 · Cited by 271 · see citing works
Self-citationDesensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation
Sayed, N., Baskaran, P., Ma, X., van den Akker, F., & Beuve, A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703944104 · Cited by 221 · see citing works
Ying, J., Clavreul, N., Sethuraman, M., Adachi, T. K., & Cohen, R. A. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.07.014 · Cited by 217 · see citing works
Dumitrescu, C., Biondi, R., Xia, Y., Cardounel, A. J., Druhan, L. J., Ambrosio, G., & Zweier, J. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702986104 · Cited by 192 · see citing works
Self-citationRoubaud, V., Sankarapandi, S., Kuppusamy, P., Tordo, P., & Zweier, J. L. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2067 · Cited by 186 · see citing works
Self-citationGiraldez, R. R., Panda, A., Xia, Y., Sanders, S. P., & Zweier, J. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21420 · Cited by 180 · see citing works
Self-citationPhosphorylation of Endothelial Nitric-oxide Synthase Regulates Superoxide Generation from the Enzyme
Chen, C., Druhan, L. J., Varadharaj, S., Chen, Y., & Zweier, J. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802269200 · Cited by 173 · see citing works
Self-citationVita, J. A., Frei, B. B., HOLBROOK, M. M., Gokce, N., Leaf, C. D., & Keaney, J. F. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1155 · Cited by 139 · see citing works
Kang, N., Cao, S., Chatterjee, S., Yao, J. Z., Egan, L. J., Semela, D., Mukhopadhyay, D., & Shah, V. H. (2007) · Journal of Cell Science · doi:10.1242/jcs.03361 · Cited by 121 · see citing works
Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall
Alzawahra, W. F., Talukder, M. A. H., Liu, X., Samouilov, A., & Zweier, J. L. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00374.2008 · Cited by 111 · see citing works
Self-citationRegulation of eNOS-Derived Superoxide by Endogenous Methylarginines
Druhan, L. J., Forbes, S. P., Pope, A. J., Chen, C.-A., Zweier, J. L., & Cardounel, A. J. (2008) · Biochemistry · doi:10.1021/bi702377a · Cited by 104 · see citing works
Self-citationKugiyama, K., Ohgushi, M., Motoyama, T., Hirashima, O., Soejima, H., Misumi, K., Yoshimura, M., Ogawa, H., Sugiyama, S., & Yasue, H. (1998) · Circulation · doi:10.1161/01.cir.97.23.2299 · Cited by 100 · see citing works
Cardounel, A. J., Xia, Y., & Zweier, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410241200 · Cited by 97 · see citing works
Self-citationThiol Dependence of Nitric Oxide Synthase
Hofmann, H., & Schmidt, H. H. H. W. (1995) · Biochemistry · doi:10.1021/bi00041a023 · Cited by 97 · see citing works
Vanin, A. F., Liu, X., Samouilov, A., Stukan, R. A., & Zweier, J. L. (2000) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(00)00033-7 · Cited by 78 · see citing works
Self-citationSite-Specific S-Glutathiolation of Mitochondrial NADH Ubiquinone Reductase
Chen, C., Zhang, L., Yeh, A., Chen, C., Green‐Church, K. B., Zweier, J. L., & Chen, Y. (2007) · Biochemistry · doi:10.1021/bi602580c · Cited by 70 · see citing works
Self-citationWang, Y., Qiao, M., Mieyal, J. J., Asmis, L. M., & Asmis, R. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.029 · Cited by 67 · see citing works
Xia, Y., Cardounel, A. J., Vanin, A. F., & Zweier, J. L. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00427-5 · Cited by 63 · see citing works
Self-citationUltrathin Cryosections: An Important Tool for Immunofluorescence and Correlative Microscopy 1
Takizawa, T., & Robinson, J. M. (2003) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540305100602 · Cited by 59 · see citing works
Glutathione Regulates Nitric Oxide Synthase in Cultured Hepatocytes
Harbrecht, B. G., Silvio, M. D., Chough, V., Kim, Y., Simmons, R. L., & Billiar, T. R. (1997) · Annals of Surgery · doi:10.1097/00000658-199701000-00009 · Cited by 51 · see citing works
Role of glutathiolation in preservation, restoration and regulation of protein function
Hill, B. G., & Bhatnagar, A. (2007) · IUBMB Life · doi:10.1080/15216540701196944 · Cited by 49 · see citing works
Glutaredoxin Mediates Akt and eNOS Activation by Flow in a Glutathione Reductase-Dependent Manner
Wang, J., Pan, S., & Berk, B. C. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.144659 · Cited by 48 · see citing works
Effects of Various Imidazole Ligands on Heme Conformation in Endothelial Nitric Oxide Synthase
Berka, V., Palmer, G., Chen, P.-F., et al. (1998) · Biochemistry · doi:10.1021/bi980133l · Cited by 36 · see citing works
Contrasting effects of thiol-modulating agents on endothelial NO bioactivity
Huang, A., Xiao, H. Q., Samii, J. M., Vita, J. A., & Keaney, J. F. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.2.c719 · Cited by 32 · see citing works
Sugiyama, T., & Michel, T. M. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00767.2009 · Cited by 26 · see citing works
Loch-Caruso, R. K., Upham, B. L., Harris, C., et al. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi208 · Cited by 17 · see citing works
Characterization of Saccharomyces cerevisiae Atm1p. Functional studies of an ABC7 type transporter
Chen, C., & Cowan, J. A. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.08.002 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409 · see citing works
Neuroinflammation and psychiatric illness
Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733 · see citing works
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Oxidative stress in the pathology and treatment of systemic lupus erythematosus
Perl, A. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2013.147 · Cited by 358 · see citing works
Janaszak-Jasiecka, A., Płoska, A., Wierońska, J. M., Dobrucki, L. W., & Kalinowski, L. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00423-2 · Cited by 358 · see citing works
Causes and consequences of cysteine S-glutathionylation
Grek, C. L., Zhang, J., Manevich, Y., Townsend, D. M., & Tew, K. D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.461368 · Cited by 312 · see citing works
Biochemical basis and metabolic interplay of redox regulation
Zhang, L., Wang, X., Cueto, R., Effi, C., Zhang, Y., Tan, H., Qin, X., Ji, Y., Yang, X., & Wang, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101284 · Cited by 308 · see citing works
eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation
Karbach, S., Wenzel, P., Waisman, A., Munzel, T., & Daiber, A. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660748 · Cited by 307 · see citing works
Helmstädter, J., Frenis, K., Filippou, K., Grill, A., Dib, M., Kalinovic, S., Pawelke, F., Kus, K., Kröller-Schön, S., Oelze, M., et al. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000615456.97862.30 · Cited by 283 · see citing works
Regulation of protein function and signaling by reversible cysteine S-nitrosylation
Gould, N., Doulias, P.-T., Tenopoulou, M., Raju, K., & Ischiropoulos, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.460261 · Cited by 274 · see citing works
Regulation of obesity and insulin resistance by nitric oxide
Sansbury, B. E., & Hill, B. G. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.016 · Cited by 274 · see citing works
Endothelial dysfunction in obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_15 · Cited by 255 · see citing works
Najjar, S., Pearlman, D. M., Devinsky, O., Najjar, A., & Zagzag, D. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-142 · Cited by 248 · see citing works
Biology of nitrogen oxides in the gastrointestinal tract
Lundberg, J. O., & Weitzberg, E. (2013) · Gut · doi:10.1136/gutjnl-2011-301649 · Cited by 200 · see citing works
Ried, K., & Fakler, P. (2014) · Integrated Blood Pressure Control · doi:10.2147/ibpc.s51434 · Cited by 198 · see citing works
Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes
Funk, S. D., Yurdagul, A., & Orr, A. W. (2012) · International Journal of Vascular Medicine · doi:10.1155/2012/569654 · Cited by 176 · see citing works
ROS signaling and redox biology in endothelial cells
Panieri, E., & Santoro, M. M. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1928-9 · Cited by 168 · see citing works
Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases
Omar, S. A., Webb, A. J., Lundberg, J. O., & Weitzberg, E. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12441 · Cited by 175 · see citing works
Sansbury, B. E., Cummins, T. D., Tang, Y., Hellmann, J., Holden, C. R., Harbeson, M. A., Chen, Y., Patel, R. P., Spite, M., Bhatnagar, A., et al. (2012) · Circulation Research · doi:10.1161/circresaha.112.266395 · Cited by 156 · see citing works
De Pascali, F., Hemann, C., Samons, K., Chen, C.-A., & Zweier, J. L. (2014) · Biochemistry · doi:10.1021/bi500076r · Cited by 131 · see citing works
Self-citationMechanisms of Sudden Cardiac Death: Oxidants and Metabolism
Yang, K.-C., Kyle, J. W., Makielski, J. C., & Dudley, S. C. (2015) · Circulation Research · doi:10.1161/circresaha.116.304691 · Cited by 127 · see citing works
Nitric Oxide in Skeletal Muscle: Role on Mitochondrial Biogenesis and Function
Tengan, C., Rodrigues, G., & Godinho, R. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131217160 · Cited by 123 · see citing works
Varadharaj, S., Kelly, O. J., Khayat, R. N., Kumar, P. S., Ahmed, N., & Zweier, J. L. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00064 · Cited by 101 · see citing works
Self-citationKnorr, M., Hausding, M., Kröller-Schuhmacher, S., Steven, S., Oelze, M., Heeren, T., Scholz, A., Gori, T., Wenzel, P., Schulz, E., et al. (2011) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.111.232058 · Cited by 100 · see citing works
Pinho-Gomes, A. C., Reilly, S., Brandes, R. P., & Casadei, B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5542 · Cited by 94 · see citing works
Galougahi, K. K., Liu, C., Gentile, C., Kok, C., Nunez, A., Garcia, A., Fry, N. A. S., Davies, M. J., Hawkins, C. L., Rasmussen, H. H., et al. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000731 · Cited by 89 · see citing works
Crabtree, M. J., Brixey, R., Batchelor, H., Hale, A. B., & Channon, K. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415992 · Cited by 83 · see citing works
Signaling by S-nitrosylation in the heart
Murphy, E., Kohr, M., Menazza, S., Nguyen, T., Evangelista, A., Sun, J., & Steenbergen, C. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.01.003 · Cited by 82 · see citing works
Chen, C.-A., De Pascali, F., Basye, A., Hemann, C., & Zweier, J. L. (2013) · Biochemistry · doi:10.1021/bi400404s · Cited by 71 · see citing works
Self-citationLuteolinidin Protects the Postischemic Heart through CD38 Inhibition with Preservation of NAD(P)(H)
Boslett, J., Hemann, C., Zhao, Y. J., Lee, H.-C., & Zweier, J. L. (2017) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.239459 · Cited by 69 · see citing works
Self-citationBoslett, J., Hemann, C., Christofi, F. L., & Zweier, J. L. (2018) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00139.2017 · Cited by 65 · see citing works
Self-citationHow widespread is stable protein S-nitrosylation as an end-effector of protein regulation?
Wolhuter, K., & Eaton, P. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.02.013 · Cited by 55 · see citing works
Wang, W.-L., Shih, Y.-T., Wei, S.-Y., & Chiu, J.-J. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01177-z · Cited by 50 · see citing works
Corti, P., Tejero, J., & Gladwin, M. T. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.020 · Cited by 13 · see citing works
- Authors
- Chen, C.-A., Wang, T.-Y., Varadharaj, S., Reyes, L. A., Hemann, C., Talukder, M. A. H., Chen, Y.-R., Druhan, L. J., & Zweier, J. L.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Zweier, Jay L.
- Venue
- Nature
- Published
- 2010-12
- Volume
- 468
- Issue
- 7327
- Pages
- 1115-1118
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3370391
- OpenAlex
- W2038965219
- Cited by
- 594
- References
- 42
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 22 · 2023: 30 · 2022: 31 · 2021: 43 · 2020: 38 · 2019: 34 · 2018: 31 · 2017: 50 · 2016: 37 · 2015: 32 · 2014: 60 · 2013: 45 · 2012: 64
- FWCI
- 31.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL083237, R01HL063744, R01-HL65608, R01HL63744, P01HL065608, R01HL38324, R01 HL83237, R01 HL103846, R01HL038324, R00HL103846, K99HL103846)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- S-glutathionylation, endothelial nitric oxide synthase, eNOS uncoupling, superoxide production, nitric oxide, oxidative stress, hypertension, endothelium-dependent vasodilation, tetrahydrobiopterin, protein thiol modification, redox regulation, vascular function, tetrahydrobiopterin deficiency
- MeSH terms
- Animals, Cattle, Cells, Cultured, Dithiothreitol, Endothelium, Vascular, Glutathione, Humans, Male, Mercaptoethanol, Mutation, Oxidation-Reduction, Rats, Inbred SHR, Rats, Inbred WKY, Vasodilation, Signal Transduction, Rats, Sprague-Dawley, Reducing Agents, Endothelial Cells, Rats, 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
