Research articles

Hornik TC, Vilalta A, Brown GC (2016) Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis. J Cell Sci. 129:65-79.

Neniskyte U, Vilalta A, Brown GC (2014) Tumour necrosis factor alpha induced neuronal loss is mediated by microglial phagocytosis. FEBS Lett. 588:2952-6.

Neher JJ, Neniskyte U, Hornik T & Brown GC (2014) Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo, Glia 62:1463-75.

Vilalta A & Brown GC (2014) Deoxyglucose prevents neurodegeneration in culture by eliminating microglia. J Neuroinflammation. 11:58.

Hornik TC, Neniskyte U & Brown GC (2014) Inflammation induces Multinucleation of Microglia via PKC inhibition of Cytokinesis, generating highly phagocytic Multinucleated Giant Cells. J. Neurochem. 128, 650-661.

Neher JJ, Emmrich JV, Fricker M, Mander PK, Thery C, Brown GC (2013) Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci 110:E4098-107.

Emmrich J. Hornik T Neher J & Brown GC (2013) Rotenone induces neuronal death by microglial phagocytosis of neurons. FEBS J. 280, 5030-5038.

Neniskyte U, Brown GC (2013) Lactadherin/MFG-E8 is essential for microglia-mediated neuronal loss and phagoptosis induced by amyloid β. J Neurochem. 126, 312-7.

Fricker M, Vilalta A, Tolkovsky AM, Brown GC (2013) Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia. J Biol Chem. 288, 9145-52.

Fricker M, Oliva-Martin MJ, Brown GC (2012) Primary phagocytosis of viable neurons by microglia activated with LPS or Abeta is dependent on calreticulin/LRP phagocytic signalling. Journal of Neuroinflammation, 13, 9.

Fricker M, Neher JJ, Zhao JW, Théry C, Tolkovsky AM, Brown GC (2012) MFG-E8 Mediates Primary Phagocytosis of Viable Neurons during Neuroinflammation. J Neurosci. 32, 2657-66.

Skemiene K, Rakauskaite G, Trumbeckaite S, Liobikas J, Brown GC, Borutaite V (2013) Anthocyanins block ischemia-induced apoptosis in the perfused heart and support mitochondrial respiration potentially by reducing cytosolic cytochrome c. Int J Biochem Cell Biol. 45, 23-9.

Neniskyte U, Neher JJ, Brown GC. (2011) Neuronal death induced by nanomolar amyloid beta is mediated by primary phagocytosis of neurons by microglia. J Biol Chem. 286:39904-13.

Neher JJ, Neniskyte U, Zhao ZW, Bal-Price A, Tolkovsky AM & Brown GC (2011) Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J. Immunol. 186, 4973-83.

Barauskaite J, Grybauskiene R, Morkuniene R, Borutaite V, Brown GC (2011) Tetramethylphenylenediamine protects the isolated heart against ischaemia-induced apoptosis and reperfusion-induced necrosis. Br J Pharmacol. 162:1136-42.

Brown GC (2010) The principle of sufficiency and the evolution of control: using control analysis to understand the design principles of biological systems. Biochem Soc Trans. 38:1210-4.

Brown RD, Burke GA, Brown GC (2009) Dependence of leukemic cell proliferation and survival on H2O2 and L-arginine. Free Radic Biol Med. 46:1211-20.

Thompson AJ, Mander PK, Brown GC. (2009) The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide. Br J Pharmacol. 158:1338-43.

Borutaite V,  Morkuniene R, Arandarcikaite O, Jekabsone A, Barauskaite J &  Brown GC. (2009) Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release. Journal of Biomedical Science 2009, 16:70.

Brown GC & Radcliffe SA (2009) Does the end of life have to be hell? Soundings 42, 67-78.

Brown GC, Borutaite V (2007) Mitochondrial regulation of caspase activation by cytochrome oxidase and tetramethylphenylenediamine (TMPD) via cytosolic cytochrome C redox state. J Biol Chem. 282, 31124-30.

Jekabsone, A., Nehrer, J., Borutaite, V. & Brown, G. C. (2007) Nitric oxide from neuronal nitric oxide synthase sensitises neurons to hypoxia-induced death via competitive inhibition of cytochrome oxidase. J. Neurochem. 103, 346-356.

Jekabsone A, Mander PK, Tickler A, Sharpe M, Brown GC. (2006) Fibrillar beta-amyloid peptide Abeta1-40 activates microglial proliferation via stimulating TNF-alpha release and H2O2 derived from NADPH oxidase: a cell culture study. J Neuroinflammation. 3:24.

Borutaite, V., Hope, H., & Brown, G. C. (2006) Arachidonate and NADPH oxidase synergise with iNOS to induce death in macrophages: mechanisms of inflammatory degeneration. Pharmacol Rep. 58: 96-102.

Bal-Price, A., Garlton, J. & Brown, G. C. (2006) Nitric oxide stimulates PC12 cell proliferation via energy depletion. Nitric Oxide 14, 238-46.

Mander, P. K., Jekabsone, A. & Brown, G. C. (2006) Microglial proliferation is regulated by hydrogen peroxide from NADPH oxidase. J. Immunol. 176, 1046-52.

Borutaite, V. & Brown, G. C. (2006) S-nitrosothiol inhibition of mitochondrial complex I causes a reversible increase in mitochondrial hydrogen peroxide production. Biochim. Biophys. Acta 1757, 562-6.

Kinsner, A., Monica Boveri, Lars Hareng, Stephanie Traub, Guy Brown, Sandra Coecke, Thomas Hartung and  Anna Bal-Price (2006) Highly purified lipoteichoic acid induced proinflammatory signalling in primary culture of rat microglia through Toll-like receptor 2: selective potentiation of nitric oxide production by muramyl dipeptide. J. Neurochem. 99, 596-607.

Mander, P., Borutaite, V., Moncada, S. & Brown G. C. (2005) Nitric oxide from glial iNOS sensitizes neurons to hypoxic death via mitochondrial respiratory inhibition. J. Neurosci. Res. 79, 208-215.

Borutaite, V., Moncada, S. & Brown, G. C. (2005) Nitric oxide from inducible nitric oxide synthase sensitizes the inflamed aorta to hypoxic damage via respiratory inhibition. Shock 23, 319-323.

Kinsner A, Pilotto V, Deininger S, Brown GC, Coecke S, Hartung T, Bal-Price A. (2005) Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation. J. Neurochem. 95, 1132-43.

Mander, P. K. & Brown, G.C. (2005) Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration. Journal of Neuroinflammation 2005, 2:20.

Jekabsone, A., Ivanoviene, L., Brown, G.C., Borutaite, V. (2003) Nitric oxide and calcium together inactivate mitochondrial complex I and induce cytochrome c release. J. Mol. Cell. Cardiol. 35. 803-809.

Borutaite, V. & Brown, G. C. (2003) Nitric oxide induces apoptosis via hydrogen peroxide, but necrosis via energy and thiol depletion. Free Rad. Biol. Med. 35, 1457-68.

Jekabsone, A., Morkuniene, R., Brown, G.C., Borutaite, V. (2003) S-nitrosothiols, but not nitric oxide, induce cytochrome c release, mitochondrial dysfunction and caspase activation in perfused heart via mitochondrial permeability transition. Biochem. Pharmacol. 66, 1513-20.

Yung, H-W., Bal-Price, A.K., Brown, G.C. & Tolkovsky A.M. (2004) Nitric oxide-induced cell death of cerebrocortical murine astrocytes is mediated through p53- and Bax-dependent pathways. J. Neurochem. 89, 812-21.

Borutaite, V., Jekabsone, A., Morkuniene, R., Brown, G.C. (2003) Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia. J. Mol. Cell. Cardiol. 35, 357-366.

Golde, S., Chandran, S., Brown, G. C. & Compston, A. (2002) Different pathways for iNOS-mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression. J Neurochem. 82, 269-82.

Bal-Price, A., Moneer, Z. & Brown, G. C. (2002) Nitric oxide induces rapid, calcium-dependent release of vesicular glutamate and ATP from cultured rat astrocytes.  Glia 40, 312-323.

Bal-Price, A. & Brown, G. C. (2002) Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production. J. Neurochem. 80, 73-80.

Stewart VC, Heslegrave AJ, Brown GC, Clark JB, Heales SJ. (2002) Nitric oxide-dependent damage to neuronal mitochondria involves the NMDA receptor. Eur J Neurosci. 15, 458-464.

Borutaite, V. & Brown, G. C. (2001) Caspases are reversibly inactivated by hydrogen peroxide. FEBS Lett. 500, 114-8.

Bal-Price, A. & Brown, G. C. (2001) Inflammatory neurodegeneration mediated by nitric oxide from activated glia, inhibiting neuronal respiration, causing glutamate release and excitoxicity. J. Neuroscience 21, 6480-6491.

Borutaite, V., Budriunaite, A., Morkuniene, R. & Brown, G. C. (2001) Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by mycocardial ischaemia. Biochim. Biophys. Acta 1537, 101-109.

Borutaite, V., Matthias, A., Harris, H., Moncada, S. & Brown, G. C. (2001) Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation. Am. J. Physiol. 281, H2256-H2260.

Kholodenko, B.N., Brown, G.C, Hoek, J.B. Diffusion control of protein phosphorylation flux in signal transduction pathways. Biochem. J. (2000), 530, 901-907.

Bal-Price, A. & Brown, G. C. (2000) Nitric oxide induced necrosis and apoptosis in PC12 cells mediated by mitochondria. J. Neurochem. 75, 1455-1464.

Borutaite, V., Budriunaite, A. & Brown, G. C. (2000) Reversal of nitric oxide-, peroxynitrite- and S-nitrosothiol-induced inhibition of mitochondrial respiration or complex I activity by light and thiols. Biochim. Biophys. Acta 1459,405-412.

Borutaite, V., Morkuniene, R. & Brown, G. C. (2000) Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms. FEBS Lett. 467, 155-159.

Brown, G. C. & Kholodenko, B. N. (1999) Spatial gradients of cellular phospho-proteins. FEBS Lett. 457, 452-454.

McBride, A. G., Borutaite, V. & Brown, G. C. (1999) Superoxide dismutase and hydrogen peroxide cause rapid nitric oxide breakdown, peroxynitrite production and subsequent cell death. Biochim. Biophys. Acta. 1454, 275-288.

Borutaite, V., Morkuniene, R. & Brown, G. C. (1999) Release of cytochrome c from heart mitochondria is induced by high calcium and peroxynitrite and is responsible for calcium-induced inhibition of substrate oxidation. Biochim. Biophys. Acta 1453, 41-48.

Clementi, E., Brown, G. C., Foxwell, N. & Moncada, S. (1999) On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc. Natl. Acad. Sci. USA 96, 1559-1562.

McNaught, K. St. P. & Brown, G. C. (1998) Nitric oxide causes glutamate release from brain synaptosomes following inhibition of mitochondrial function. J. Neurochem. 70, 1541-1546.

Clementi, E., Brown, G. C., Feelisch, M. & Moncada, S. (1998) Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc. Natl. Acad. Sci. 95, 7631-7636.

Soboll, S., Oh, M-H. & Brown, G. C. (1998) Control of oxidative phosphorylation, gluconeogenesis, ureagenesis and ATP turnover in isolated perfused rat liver analysed by top-down metabolic control analysis. Eur. J. Biochem. 254, 194-201.

Kholodenko, B. N., Hoek, J. B., Brown, G. C. & Westerhoff, H. V. (1998) Control analysis of cellular signal transduction pathways. In: BioThermoKinetics in the Post Genomic Era (Larsson, C et al. eds.) Chalmers Reproservice, Gotenberg.

Brown, G. C. (1998) Evolutionary implications of metabolic control analysis for maximisation of rates of enzymes, pathways and physiological processes by natural selection. In: BioThermoKinetics in the Post Genomic Era (Larsson, C et al. eds.) Chalmers Reproservice, Gotenberg.

Korzeniewski, B. & Brown, G. C. (1998) Quantification of the relative contribution of parallel pathways to signal transfer: application to cellular energy transduction.  Biophysical Chemistry 75, 73-80.

Brown, G. C., Foxwell, N. & Moncada, S. (1998) Transcellular regulation of cell respiration by nitric oxide generated by activated macrophages.  FEBS Lett.439, 321-324.

Brown, G. C., Hoek, J. B. & Kholodenko, B. N. (1997) Why do protein kinase cascades have more than one level? Trends Biochem. Sci. 22, 288.

Kholodenko, B. N., Hoek, J. B., Westerhoff, H. V. & Brown, G. C. (1997) Quantification of information transfer via cellular signal transduction pathways.  FEBS Lett. 414, 430-434.

McBride, A. G. & Brown, G. C. (1997) Activation of human neutrophils causes rapid nitric oxide breakdown. FEBS Lett. 417, 231-234.

Penrice, J., Lorek, A., Cady, E. B., Amess, P. N., Wylezinska, M., Cooper, C. E., D'Souza, P., Brown, G. C., Kirkbride, V., Edwards, A. D., Wyatt, J. S. & Reynolds, E. O. R. (1997) Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet Pediatr. Res. 41, 795-802.

Borutaite, V., Morkuniene, R., Budriunaite, A., Krasauskaite, D., Ryselis, S., Toleikis, A. & Brown, G. C. (1996) Kinetic analysis of changes in activity of heart mitochondrial oxidative phosphorylation system induced by ischaemia. J. Mol. Cell. Cardiol. 28, 2195-2201.

Mildaziene, V., Baniene, R., Nauciene, Z., Marcinkeviciute, A., Borutaite, V., Kholodenko, B. & Brown, G. C. (1996) Ca2+ stimulates both respiratory and phosphorylation subsystems in heart mitochondria. Biochem. J. 320, 329-334.

Kholodenko, B. N. & Brown, G. C. (1996) Paradoxical control properties of enzymes within pathways: can activation cause an enzyme to have increased control? Biochem. J. 314, 753-760.

Borutaite, V. & Brown, G. C. (1996) Mitochondria rapidly reduce nitric oxide, and nitric oxide reversibly inhibits mitochondrial respiration. Biochem. J. 315, 295-299.

Brown, G.C. (1996) Information transfer via energy transducing pathways: Control of ATP turnover by ATP production. In: BioThermoKinetics of the Living Cell (eds H.V. Westerhoff et al.) pp. 71-74.

Kholodenko, B.N. & Brown, G.C. (1996) Extension of metabolic control analysis to physiology: control by body organs in vivo. In BioThermoKinetics of the Living Cell (eds H.V. Westerhoff et al.) pp. 163-167.

Mildaziene, V., Baniene, R., Nauciene, Z., Baker, B. M., Brown, G. C., Westerhoff, H. V. & Kholodenko, B. N. (1995) Calcium indirectly increases the control exerted by the adenine nucleotide translocator over 2-oxoglutarate oxidation in rat heart mitochondria. Archiv. Biophys. Biochem. 324, 130-134.

Brown, G. C. (1995) Reversible binding and inhibition of catalase by nitric oxide. Eur. J. Biochem. 232, 188-191.

Borutaite, V., Mildaziene, V., Brown, G. C. & Brand, M. D. (1995) Control and kinetic analysis of ischaemia-damaged heart mitochondria: which parts of the oxidative phosphorylation system are affected by ischemia? Biochim. Biophys. Acta 1272, 154-158.

Thorenson, M., Penrice, J., Lorek, A., Cady, E. B., Wylezinska, M., Kirkbride, V., Cooper, C. E., Brown, G. C., Edwards, A. D., Wyatt, J. S. & Reynolds, E. O. R. (1995) Mild hypothermia following severe transient hypoxia-ischaemia ameliorates delayed cerebral energy failure in the new born piglet. Pediatric Research, 37, 667-670.

Brown, G. C. (1995) Rate control within the Na+/glucose cotransporter. Biophys. Chem. 54, 181-189.

Brown, G. C., Bolanos, J. P., Heales, S. J. R. & Clark, J. B. (1995) Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neuroscience Lett. 193, 201-204.

Cooper, C. E. & Brown, G. C. (1995) The interaction between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance. Biochem. Biophys. Res. Commun. 212, 404-412.

Mehmet, H. Yue, X., Squier, M. V., Cady, E., Penrice, J., Sarraf, C., Wylezinska, M., Kirkbride, V., Cooper, C., Brown, G. C., Wyatt, J. S., Reynolds, E. O. R. & Edwards, A. D. (1994) Increased apoptosis in the cingulate sulcus of newborn piglets following transient hypoxia-ischaemia is related to the degree of high energy phosphate depletion during the insult. Neuroscience Lett. 181, 121-125.

Cady, E. B., Lorek, A., Penrice, J., Wylezinska, M., Cooper, C. E., Brown, G. C., Owen-Rice, H., Kirkbride, V., Wyatt, J. S.,Reynolds, E. O. R. (1994) Brain-metabolite transverse relaxation times in magnetic resonance spectroscopy increase as adenosine triphosphate depletes during secondary energy failure following hypoxia-ischaemia in the newborn piglet. Neuroscience Lett. 182, 201-204.

A.Loreck, Y.Takei, E.B.Cady, J.S.Wyatt, J.Penrice, A.D.Edwards, D.Peebles, M.Wylezinska, H.Owen-Reece, V.Kirkbride, C.E.Cooper, R.F.Aldridge, S.C.Roth, G.C. Brown, D.T.Delpy, & E.O.R.Reynolds (1994) Delayed ('secondary') cerebral energy failure following acute hypoxia-ischaemia in the newborn piglet: continuous 48-hour studies by phosphorous magnetic resonance spectroscopy. Pediatric Research 36, 699-706.

Brown, G. C. & Cooper, C. E. (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 356, 295-298.

Brown, G. C. (1994) Control analysis applied to the whole body: control by body organs over plasma concentrations and organ fluxes of substances in the blood, Biochem. J. 297, 115-122.

Brown, G. C. & Cooper, C. E. (1994) The analysis of rate-limitation within enzymes: relations between flux control coefficients of rate constants and unidirectional rates, rate constants and thermodynamic parameters of single isolated enzymes. Biochem. J. 300, 159-164.

Kholodenko, B. N., Westerhoff, H. V. & Brown, G. C. (1994) Rate limitation within a single enzyme is directly related to enzyme intermediate levels, FEBS Lett. 349, 131-134.

McCormick, D. C., Edwards, A. D., Brown, G. C., Wyatt, J. S., Potter, A., Cope, M., Delpy, D. T. & Reynolds, E. O. R.(1993) Effect of Indomethacin on Cerebral Oxidised Cytochrome Oxidase in Preterm Infants, Pediatric Research 33, 603-608.

Brown, G. C. & Cooper, C. E. (1993) Control analysis applied to single enzymes: can an isolated enzyme have a unique rate-limiting step?, Biochem. J. 294, 87-94.

Brown, G. C. (1991) Total cell protein concentration as an evolutionary constraint on the metabolic control distribution in cells, J. theor. Biol. 153, 195-203.

Edwards, A. D., Brown, G. C., Cope, M., Wyatt, J. S., McCormick, D. C., Roth, D. T. & Reynolds, E. O. R. (1991) Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase, J. Appl. Physiol. 71, 1907-1913.

Brown, G. C., Crompton, M. & Wray, S. (1991) Cytochrome oxidase content of rat brain during development, Biochim. Biophys. Acta 1057, 273-275.

Brown, G. C. & Brand, M. D. (1991) On the nature of the mitochondrial proton leak. Biochim. Biophys. Acta 1059, 55-62.

Brown, G. C. (1990) Electrostatic coupling between membrane proteins, FEBS Lett. 260, 1-5.

Brown, G. C., Hafner, R. P. & Brand, M. D. (1990) A top-down approach to the determination of control coefficients in metabolic control theory, Eur. J. Biochem. 188, 321-319.

Hafner, R. P., Brown, G. C. & Brand, M. D. (1990) Analysis of the control of respiration rate, phosphorylation rate, proton leak rate and proton motive force in isolated mitochondria using the top-down approach of metabolic control theory, Eur. J. Biochem. 188, 313-319.

Nobes, C. D., Brown, G. C., Olive, P. N. & Brand, M. D. (1990) Non-ohmic proton conductance of the mitochondrial inner membrane in hepatoytes, J. Biol. Chem. 265, 12903-09.

Brown, G. C., Lakin-Thomas, P. L. & Brand, M. D. (1990) Control of respiration and oxidative phosphorylation in isolated liver cells, Eur. J. Biochem. 192, 355-362.

Hafner, R. P., Brown, G. C. & Brand, M. D. (1990) Thyroid hormone control of state-3 respiration in isolated rat liver mitochondria, Biochem. J. 265, 731-734.

Brown, G. C. (1989) The relative proton stoichiometries of the mitochondrial proton pumps are independent of the protonmotive force. J. Biol. Chem. 264, 14704-09.

Brown, G. C. & Brand, M. D. (1988) Proton/electron stoichiometry of mitochondrial complex I estimated from the equilibrium thermodynamic force ratio. Biochem. J. 252, 473-479.

Brand, M. D., Hafner, R. P. & Brown, G. C. (1988). Control of respiration in non-phosphorylating mitochondria is shared between the proton leak and the respiratory chain. Biochem. J. 255, 535-539.

Brown, G. C. & Brand, M. D. (1986). Changes in permeability to protons and other cations at high proton motive force in rat liver mitochondria. Biochem. J. 234, 75-81.

Murphy, M. P., Brown, G. C. & Brand, M. D. (1985) Thermodynamic limits to the stoichiometry of H+ pumping by mitochondrial cytochrome oxidase. FEBS Lett. 187, 16-20.

Brown, G. C. & Brand, M. D. (1985) Thermodynamic control of flux through mitochondrial cytochrome bc1 complex. Biochem. J. 225, 399-405.

Brand, M. D., Al-Shawi, M. K., Brown, G. C. & Price, B. D. (1985). Thermodynamic and steady-state-kinetic investigation of the effect of NN'-dicyclohexylcarbodi-imide on H+ translocation by the mitochondrial cytochrome bc1 complex. Biochem. J. 225, 407-411.