Magnifico 2011 Abstract IOC61
|Magnifico MC, Arese M, Mastronicola D, Forte E, Giuffre A, Testa F, Sarti P (2011) NO-signalling and cell bioenergetics. MiPNet16.01.|
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.
 Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356: 295-298.  Sarti P et al (2000) Nitric oxide and cytochrome c oxidase: mechanisms of inhibition and NO degradation. Biochim Biophis Res Com 274: 183.  Sarti P et al (2003) Nitric oxide and cytochrome oxidase: reaction mechanisms from the enzyme to the cell. Free Radic Biol Med 34: 509-520.  Mason MG et al (2006) Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase. Proc Natl Acad Sci U S A 103: 708.  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: 2991-2997.
• O2k-Network Lab: IT Rome Sarti P
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Intact cells Enzyme: Complex IV;cytochrome c oxidase Regulation: Inhibitor, Oxygen kinetics Coupling state: OXPHOS
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.