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Magnifico 2011 Abstract IOC61

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Magnifico MC, Arese M, Mastronicola D, Forte E, Giuffre A, Testa F, Sarti P. (2011) NO-signalling and cell bioenergetics. IOC61.

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Magnifico MC, Arese M, Mastronicola D, Forte E, Giuffre A, Testa F, Sarti P. (2011)

Event: IOC61

Nitric oxide (NO) is a biological messenger which regulates several physiological responses including relaxation of smooth muscle, neurotransmission, inhibition of platelet aggregation, cell migration and mitochondrial respiration. In mammals NO is synthesized by three different gene-encoded NO synthase (NOS), the neuronal NOS (nNOS or NOS1), the inducible NOS (iNOS or NOS2), the endothelial NOS (eNOS or NOS3) and possibly a mitochondrial NOS. Made available exogenously or endogenously, NO reacts with heamoproteins such as guanylate cyclase, haemoglobin, myoglobin and cytochrome c oxidase (CcOX).

     The NO-CcOX interaction is of particular interest, being rapid and reversible and leading to changes of the ATP synthesis (1). Inhibition may or may not occur in competition with O2, particularly depending on substrates availability (e-, O2) (2). Experimental evidence suggests that NO might be a physiological regulator of cell respiration turning to pathological under circumstances (3-4). Many effectors have been shown to control the enzymatic activity of the NOSs, thus the cell bioavailability of NO. We have focused our attention on the effects of compounds likely involved in the regulation of the level of NO endogenously produced in the cells, such as morphine, melatonin, hydrocortisone (5). Under a number of conditions we have measured the NOSs expression and tentatively correlated the observation to nitrate-nitrite accumulation and parameters of  mitochondrial efficiency.

(1) 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. (2) Sarti P. et al. (2000) Nitric oxide and cytochrome c oxidase: mechanisms of inhibition and NO degradation. Biochim. Biophis. Res. Com. 274:183. (3) Sarti P. et al. (2003) Nitric oxide and cytochrome oxidase: reaction mechanisms from the enzyme to the cell. Free Radic. Biol. Med. 34(5):509-20. (4) Mason M.G. et al. (2006) Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase. Proc. Natl. Acad. Sci. USA. 103: 708. (5) Mastronicola D. et al. (2004) Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells. Cell. Mol. Life Sci. 61: 2991-7.

β€’ Keywords: nitric oxide; mitochondrial bioenergetics; cytochrome c oxidase; cell respiration.

β€’ O2k-Network Lab: IT Roma Sarti P


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Organism: Human  Tissue;cell: Endothelial; Epithelial; Mesothelial Cell"Endothelial; Epithelial; Mesothelial Cell" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.  Preparation: Intact Cell; Cultured; Primary"Intact Cell; Cultured; Primary" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.  Enzyme: Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Coupling; Membrane Potential"Coupling; Membrane Potential" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 


HRR: Oxygraph-2k, Spectrophotometry; Spectrofluorimetry"Spectrophotometry; Spectrofluorimetry" is not in the list (Oxygraph-2k, TIP2k, O2k-Fluorometer, pH, NO, TPP, Ca, O2k-Spectrophotometer, O2k-Manual, O2k-Protocol, ...) of allowed values for the "Instrument and method" property. 


Magnifico MC (1), Arese M (1,2), Mastronicola D (3), Forte E (1,2), Giuffre A(3), Testa F (1), Sarti P (1,2).

(1) Department of Biochemical Sciences,Sapienza University of Rome. (2) The second Faculty of Medicine, S. Andrea Hospital, Sapienza University of Rome. (3) CNR-Institute of Molecular Biology and Pathology, Rome.