Research Topics
| Salvador MoncadaSummaryAffiliation: University College London Country: UK Publications
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Publications
Nitric oxide, cell bioenergetics and neurodegenerationSalvador Moncada
The Wolfson Institute for Biomedical Research, University College London, London, UK
J Neurochem 97:1676-89. 2006..Thus, whilst NO plays a physiological role in neuronal cell signalling, its over-production may cause neuronal energy compromise leading to neurodegeneration...- Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxideMiriam Palacios-Callender
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK
J Cell Sci 120:160-5. 2007..We suggest that this is a physiological mechanism regulated by the flux of electrons in the mitochondria and by the changing ratio of O2:NO, either during hypoxia or, as a consequence of increases in NO, as a result of cell stress... 
Inactivation of nitric oxide by cytochrome c oxidase under steady-state oxygen conditionsDavid C Unitt
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Biochim Biophys Acta 1797:371-7. 2010..At both high and low O(2) concentrations the inactivation of NO is decreased when sodium azide is used to inhibit cytochrome c oxidase and decrease electron turnover...
Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury?Alexander Galkin
Wolfson Institute for Biomedical Research, University College London, Gower Street, London, UK
J Biol Chem 284:36055-61. 2009..These observations provide a mechanism to account for the severe cell injury that follows hypoxia and reoxygenation when accompanied by NO generation...- Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiolThilo Hagen
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Biochem Biophys Res Commun 322:923-9. 2004..Since these actions of 2ME2 occur at higher concentrations than those known to inhibit cell proliferation, it remains to be established whether they contribute to its therapeutic effect... - Nitric oxide: orchestrating hypoxia regulation through mitochondrial respiration and the endoplasmic reticulum stress responseWeiming Xu
Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, Gower Street, London, WC1E 6BT, UK
Cell Res 15:63-5. 2005.... - Mitochondrial dysfunction and HIF1alpha stabilization in inflammationAssegid Garedew
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
J Cell Sci 121:3468-75. 2008..Nevertheless, the amount of ATP generated is not sufficient to fulfil the energy requirements of the activated cells, probably leading to a progressive energy deficit with the consequent inhibition of cell proliferation and death... - Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: a possible explanation for hypoxic vasodilationMiriam Palacios Callender
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom
Proc Natl Acad Sci U S A 104:18508-13. 2007..The resultant increase in NO concentration could explain hypoxic vasodilation... - Inhibition of cellular respiration by endogenously produced carbon monoxideGabriela D'Amico
Wolfson Institute for Biomedical Research, University College London, UK
J Cell Sci 119:2291-8. 2006..Inhibition of cell respiration by endogenous CO through its interaction with cytochrome c oxidase might have an important role in inflammatory and hypoxic conditions... - Nitric oxide and hypoxiaAlexander Galkin
The Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6BT, U K
Essays Biochem 43:29-42. 2007..This chapter discusses the physiological and pathophysiological implications of the interactions of NO with the cytochrome c oxidase... - Mitochondrial dynamics, biogenesis, and function are coordinated with the cell cycle by APC/C CDH1Assegid Garedew
Wolfson Institute for Biomedical Research, University College London, London, UK
Cell Metab 15:466-79. 2012..Thus, we have identified an important component of the molecular mechanism that coordinates cell proliferation with activation of the mitochondrial metabolic machinery that provides the necessary energy and biosynthetic substrates... - AMPKalpha1 regulates the antioxidant status of vascular endothelial cellsSergio L Colombo
Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London WC1E6AE, UK
Biochem J 421:163-9. 2009.... - S-nitrosation of mitochondrial complex I depends on its structural conformationAlexander Galkin
Wolfson Institute for Biomedical Research, University College London, London, UK
J Biol Chem 282:37448-53. 2007..The implications of this finding for hypoxic or pathophysiological conditions in vivo are discussed... - Hypoxia accelerates nitric oxide-dependent inhibition of mitochondrial complex I in activated macrophagesMatthew T Frost
Wolfson Institute for Biomedical Research, University College London, Gower St, London WC1E 6BT, UK
Am J Physiol Regul Integr Comp Physiol 288:R394-400. 2005..Our results suggest that hypoxia amplified the mitochondrial inhibition induced by NO generated during inflammatory disease states... - Sir John Robert Vane: 29 March 1927 - 19 November 2004Salvador Moncada
The Wolfson Institute for Biomedical Research, University College London
Biogr Mem Fellows R Soc 52:401-11. 2006..During his distinguish career he published more than 700 scientific papers and wrote or editing 20 books. His many awards include the Nobel Prize in Physiology or Medicine (1982) and a knighthood in 1984... - Fulfilling the metabolic requirements for cell proliferationSalvador Moncada
Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK
Biochem J 446:1-7. 2012..These findings have implications for the understanding of cell proliferation in general and, in particular, of cancer, its prevention and treatment... - Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice: key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivoRamona S Scotland
Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
Circulation 111:796-803. 2005.... - Two phases of nitrergic neuropathy in streptozotocin-induced diabetic ratsSelim Cellek
Wolfson Institute for Biomedical Research, University College London, London, UK
Diabetes 52:2353-62. 2003..Neurodegeneration is due to apoptotic cell death in the ganglia, which is selective for the nitrergic neurones... - Obituary: John R. Vane (1927-2004)Salvador Moncada
Salvador Moncada is at the Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.e-mail
Nature 433:28. 2005 - Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy productionJuan M Funes
Cancer Research U K Viral Oncology Group, University College London, London WC 1E 6BT, UK
Proc Natl Acad Sci U S A 104:6223-8. 2007..We did find, however, a reversible increase in the transcription of glycolytic enzymes in tumors generated by transformed MSC, indicating this is a secondary phenomenon resulting from adaptation of the tumor to its microenvironment... - Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formationMarisol Quintero
The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, London WC1E 6BT, UK
Cancer Res 66:770-4. 2006..We suggest that, in certain forms of cancer, NO might be responsible for the accumulation of HIF-1alpha by a mechanism dependent on free radicals... - Adventures in pharmacology, aspirin, prostacyclin and nitric oxideSalvador Moncada
Wolfson Institute for Biomedical Research, University College London, London, UK
Acta Cardiol 59:47-50. 2004 - Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic reticulum stress responseWeiming Xu
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK
Nat Cell Biol 6:1129-34. 2004..The NO-mediated ER stress response is diminished in rho(0) cells devoid of mitochondrial DNA, consistent with our evidence that NO-dependent mitochondrial disruption is coupled to the ER stress response... - Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alphaThilo Hagen
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Science 302:1975-8. 2003..Thus, the signaling consequences of hypoxia may be profoundly modified by nitric oxide... - Monitoring cytochrome redox changes in the mitochondria of intact cells using multi-wavelength visible light spectroscopyVeronica S Hollis
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6AE, UK
Biochim Biophys Acta 1607:191-202. 2003..Here we describe this novel methodology and demonstrate its validity by monitoring the action of known respiratory chain inhibitors, including the endogenous signalling molecule NO, on cytochrome redox states in human leukocytes... - Does nitric oxide modulate mitochondrial energy generation and apoptosis?Salvador Moncada
The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Nat Rev Mol Cell Biol 3:214-20. 2002.... - Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272Adrian J Hobbs
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6AE, UK
Vascul Pharmacol 40:149-54. 2003.... - Increased expression of arginase II in patients with different forms of arthritis. Implications of the regulation of nitric oxideInes Corraliza
Wolfson Institute for Biomedical Research, University College London, London, UK
J Rheumatol 29:2261-5. 2002..To investigate the expression of arginase isoforms in patients with different forms of arthritis and the possible implications of the synthesis of nitric oxide (NO)... - Discrepancies between nitroglycerin and NO-releasing drugs on mitochondrial oxygen consumption, vasoactivity, and the release of NOCristina Nunez
Departamento de Farmacologia, Facultad de Medicina, Universidad de Valencia, Blasco Ibañez, Valencia, Spain
Circ Res 97:1063-9. 2005.... - Does nitric oxide allow endothelial cells to sense hypoxia and mediate hypoxic vasodilatation? In vivo and in vitro studiesNicholas J Edmunds
Department of Physiology, The Medical School, The University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK
J Physiol 546:521-7. 2003..We propose that in vivo, shear-released NO increases the apparent K(m) of endothelial cytochrome oxidase for O(2), allowing the endothelium to act as an O(2) sensor, releasing adenosine in response to moderate falls in O(2)... - TNF-alpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodentsAlessandra Valerio
Integrated Laboratories Network, Center for Study and Research on Obesity, Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy
J Clin Invest 116:2791-8. 2006..Our findings demonstrate that TNF-alpha impairs mitochondrial biogenesis and function in different tissues of obese rodents by downregulating eNOS expression and suggest a novel pathophysiological process that sustains obesity... - Mitochondria as signaling organelles in the vascular endotheliumMarisol Quintero
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6AE, U.K
Proc Natl Acad Sci U S A 103:5379-84. 2006..Diversion of O(2) away from endothelial cell mitochondria by NO might also facilitate oxygenation of vascular smooth muscle cells... - Nitric oxide and mitochondrial signaling: from physiology to pathophysiologyJorge D Erusalimsky
Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Cardiff, CF5 2YB, UK
Arterioscler Thromb Vasc Biol 27:2524-31. 2007..We also discuss instances in which the effects of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology... - Pioneers in cardiology: Salvador Moncada, MD, PhD, FRSEmma Baines
Circulation 114:f185-6. 2006 - Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOSEnzo Nisoli
Integrated Laboratories Network, Department of Preclinical Sciences, Luigi Sacco Hospital, Milan University, 20157 Milan, Italy
Science 310:314-7. 2005..These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals... - Mitochondrial biogenesis in mammals: the role of endogenous nitric oxideEnzo Nisoli
Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy
Science 299:896-9. 2003..Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance... - BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitroJas S Kalsi
Wolfson Institute for Biomedical Research, University College London, United Kingdom
J Urol 169:761-6. 2003..3 to 3 microM. BAY41-2272. CONCLUSIONS: We report that a nonNO based soluble guanylate cyclase activator relaxes human and rabbit corpus cavernosum, and potentiates nitrergic responses... - Macrophage endothelial nitric-oxide synthase autoregulates cellular activation and pro-inflammatory protein expressionLinda Connelly
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095, USA
J Biol Chem 278:26480-7. 2003.... - NCX-4016, a nitric oxide-releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial functionStefano Fiorucci
Dipartimento di Medicina Clinica e Sperimentale, Clinica di Gastroenterologia ed Epatologia, Universita degli Studi di Perugia, 06122 Perugia, Italy
FASEB J 16:1645-7. 2002..In contrast to DETA-NO, NCX-4016 did not increase mitochondrial oxidative stress. These data demonstrated that NCX-4016 conveys NO directly inside endothelial cells and modulates mitochondrial function... - Inhibition of mitochondrial respiration by endogenous nitric oxide: a critical step in Fas signalingBelen Beltran
Centro Nacional de Investigaciones Cardiovasculares, C Sinesio Delgado, 6 Pab 5 28029 Madrid, Spain
Proc Natl Acad Sci U S A 99:8892-7. 2002..The significance of the two phases in relation to cell survival and death remains to be studied... - Mitochondrial biogenesis as a cellular signaling frameworkEnzo Nisoli
Center for Study and Research on Obesity, Department of Preclinical Sciences, LITA Vialba, Luigi Sacco Hospital, University of Milan, Via G B Grassi 74, 20157, Milan, Italy
Biochem Pharmacol 67:1-15. 2004..Some of these are now being elucidated. Generation of nitric oxide (NO) appears to be a novel player in this scenario, possibly acting as a unifying molecular switch to trigger the whole mitochondriogenic process... - Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathwayAngeles Almeida
, Hospital Universitario de Salamanca, 37007 Salamanca, Spain
Nat Cell Biol 6:45-51. 2004..Thus the virtual absence of PFK2 in neurons may explain their extreme sensitivity to energy depletion and degeneration... - Salvador MoncadaKaren Birmingham
Nat Med 8:98. 2002 - Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitmentAmrita Ahluwalia
William Harvey Research Institute, Barts and The London, Charterhouse Square, London EC1M 6BQ, United Kingdom
Proc Natl Acad Sci U S A 101:1386-91. 2004..These data demonstrate that sGC plays a key antiinflammatory role by inhibiting P-selectin expression and leukocyte recruitment... - Endogenous NO regulates superoxide production at low oxygen concentrations by modifying the redox state of cytochrome c oxidaseMiriam Palacios-Callender
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6BT, United Kingdom
Proc Natl Acad Sci U S A 101:7630-5. 2004..This, in turn, favors the release of O(2)(-), which initiates the transcriptional activation of NF-kappa B as an early signaling stress response... - Can endogenous gaseous messengers control mitochondrial biogenesis in mammalian cells?Enzo Nisoli
Department of Preclinical Sciences, Center for Study and Research on Obesity, LITA Vialba, Luigi Sacco Hospital, University of Milan, Via G B Grassi 74, 20157 Milan, Italy
Prostaglandins Other Lipid Mediat 73:9-27. 2004..Some of these are now being elucidated. Generation of nitric oxide (NO) appears to be a novel player in this scenario, possibly acting as a unifying molecular switch to trigger the whole process of the mitochondrial biogenesis... - Mitochondrial biogenesis by NO yields functionally active mitochondria in mammalsEnzo Nisoli
Department of Preclinical Sciences, Laboratorio Interdisciplinare Technologie Avanzate LITA Vialba, University of Milan, 20157 Milan, Italy
Proc Natl Acad Sci U S A 101:16507-12. 2004..We conclude that NO/cGMP stimulates mitochondrial biogenesis, both in vitro and in vivo, and that this stimulation is associated with increased mitochondrial function, resulting in enhanced formation of ATP... - Nitric oxide from inflammatory-activated glia synergizes with hypoxia to induce neuronal deathPalwinder Mander
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom
J Neurosci Res 79:208-15. 2005..Brain inflammation can thus sensitize to hypoxia-induced death, which may be important in pathologies such as stroke, neurodegeneration, and brain aging... - Regulation of hypoxia-inducible factor-1alpha by nitric oxide through mitochondria-dependent and -independent pathwaysJesús Mateo
Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III CNIC, c Sinesio Delgado 4, 28029 Madrid, Spain
Biochem J 376:537-44. 2003..We suggest that, although stabilization of HIF-1alpha by high concentrations of NO might have implications in pathophysiological processes, the inhibitory effect of lower NO concentrations is likely to be of physiological relevance... - Nitric oxide from inducible nitric oxide synthase sensitizes the inflamed aorta to hypoxic damage via respiratory inhibitionVilmante Borutaite
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
Shock 23:319-23. 2005..This NO-induced sensitization of aorta to mild hypoxia may be important in sepsis and other pathologies where iNOS is expressed... - From pollutant gas to biological messenger: the diverse actions of nitric oxide in cancerPeter A Brennan
Maxillofacial Department, Poole Hospital, Dorset, UK
Ann R Coll Surg Engl 84:75-8. 2002..This review summarises the brief history of this molecule, gives an overview of its many effects in the common solid tumours and discusses how targeting of NO production may have possible future therapeutic benefit... - Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosisArnold G Herman
Division of Pharmacology, University of Antwerpen, Campus Drie Eiken, Wilrijk, B 2610 Antwerpen, Belgium
Eur Heart J 26:1945-55. 2005.... - Activation of endothelial nitric-oxide synthase by tumor necrosis factor-alpha: a novel pathway involving sequential activation of neutral sphingomyelinase, phosphatidylinositol-3' kinase, and AktRico Barsacchi
Vita Salute University DIBIT H San Raffaele Institute, Milan, Italy
Mol Pharmacol 63:886-95. 2003..The novel pathway of activation of eNOS described here may have broad biological relevance because neutral sphingomyelinase is activated not only by TNF-alpha but also by a variety of other physiological and pathological stimuli... - Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wallTom Ziessen
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT
Br J Pharmacol 135:546-54. 2002..These results suggest that a neuronal factor elicits non-nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established... - Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cellsRowland W Rees
Wolfson Institute for Biomedical Research, University College London, United Kingdom
J Urol 170:2517-22. 2003..We suggest a novel use for Rho-kinase inhibitors in the treatment of BPH as a single agent with dual action... - Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome?Enzo Nisoli
Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Milan, Italy
Circ Res 100:795-806. 2007..Here we summarize some recent findings and propose a hypothesis for the high cardiovascular risk linked to the metabolic syndrome... - The contribution of Salvador Moncada to our understanding of the biology of nitric oxideEmilio Clementi
Dept Pharmaco Biology, University of Calabria, 87036 Rende, E Medea Scientific Institute, 23842 Bosisio Parini, Italy
IUBMB Life 55:563-5. 2003..This review article will lead the reader through the landmark events in this adventure, highlighting the fundamental role played by Salvador Moncada and his team. - GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivoWendy K Alderton
Respiratory and Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline Research, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
Br J Pharmacol 145:301-12. 2005.... - The deleterious effect of high concentrations of D-glucose requires pro-inflammatory preconditioningNuria Lafuente
Departamento de Farmacologia y Terapeutica, Facultad de Medicina, Universidad Autonoma de Madrid, Spain
J Hypertens 26:478-85. 2008..The present study investigated whether high concentrations of D-glucose can trigger pro-inflammatory mechanisms in human aortic smooth muscle cells...