title: Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells.
abstract: Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Micol
authors.identifier: 0000-0002-1020-1848
authors.initials: M
authors.lastname: Falabella
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Elena
authors.identifier: 0000-0001-9049-6916
authors.initials: E
authors.lastname: Forte
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Maria Chiara
authors.identifier: 0000-0002-0443-2674
authors.initials: MC
authors.lastname: Magnifico
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Santini
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Marzia
authors.identifier: 0000-0002-6140-2287
authors.initials: M
authors.lastname: Arese
authors.affiliation: CNR Institute of Molecular Biology and Pathology, 00185 Rome, Italy.
authors.forename: Alessandro
authors.identifier: 0000-0001-5301-0681
authors.initials: A
authors.lastname: Giuffrè
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
authors.forename: Kristina
authors.identifier: 0000-0001-5792-5061
authors.initials: K
authors.lastname: Radić
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Luciana
authors.identifier: 0000-0003-2083-8655
authors.initials: L
authors.lastname: Chessa
authors.affiliation: Centre for Experimental Neurological Therapies, S. Andrea Hospital-Site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Giulia
authors.identifier: 0000-0002-7824-8343
authors.initials: G
authors.lastname: Coarelli
authors.affiliation: Centre for Experimental Neurological Therapies, S. Andrea Hospital-Site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Maria Chiara
authors.identifier: 0000-0002-4839-1528
authors.initials: MC
authors.lastname: Buscarinu
authors.affiliation: Centre for Experimental Neurological Therapies, S. Andrea Hospital-Site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Rosella
authors.identifier: 0000-0001-5842-3100
authors.initials: R
authors.lastname: Mechelli
authors.affiliation: Centre for Experimental Neurological Therapies, S. Andrea Hospital-Site, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Marco
authors.identifier: 0000-0002-0501-8803
authors.initials: M
authors.lastname: Salvetti
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Paolo
authors.identifier: 0000-0002-8219-4827
authors.initials: P
authors.lastname: Sarti
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000328:Adult; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D005470:Fluorometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D009154:Mutation; D009573:Nitrites / Q000737:chemistry; D009584:Nitrogen; D029242:Optic Atrophy, Hereditary, Leber / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010100:Oxygen; D010101:Oxygen Consumption; D026361:Reactive Nitrogen Species / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D009573:Nitrites; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D000255:Adenosine Triphosphate; D009584:Nitrogen; D010100:Oxygen