title: Analysis of opa1 isoforms expression and apoptosis regulation in autosomal dominant optic atrophy (ADOA) patients with mutations in the opa1 gene.
abstract: Autosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy characterized by bilateral symmetrical visual loss, decrease in retinal ganglion cells and a loss of myelin within the optic nerve. ADOA is associated to mutations in Optic atrophy 1 gene (OPA1), which encodes a mitochondrial protein involved in cristae remodeling, maintenance of mitochondrial membrane integrity, mitochondrial fusion and apoptosis regulation. We thus evaluated the rate of apoptosis and the expression levels of OPA1 isoforms in ADOA and control cells. Peripheral blood lymphocytes from eight patients with OPA1 mutation and age matched controls were cultivated both in basal conditions or with 2-deoxy-D-ribose, a reducing sugar that induces apoptosis through oxidative stress. Apoptosis was analyzed by flow cytometry, phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation. We also analyzed the expression levels of OPA1 isoforms in ADOA and control cells cultured with and without 2-deoxy-D-ribose. We showed an increased percentage of apoptotic cells in ADOA patients compared to controls, both in basal culture conditions and after 2-deoxy-D-ribose treatment. This suggested a great susceptibility of ADOA cells to oxidative stress and a strong correlation between OPA1 protein dysfunctions and morphological-functional alterations to mitochondria. Moreover OPA1 protein expression was significantly decreased in lymphocytes from the ADOA patients after 2-deoxy-D-ribose treatment, implying a great sensitivity of the mutated protein to free radical damage. Concluding, we could confirm that oxidative stress-induced apoptosis may play a key role in the pathophysiological process bringing to retinal ganglion cells degeneration in ADOA.
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Patrizia
authors: P
authors: Formichi
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Elena
authors: E
authors: Radi
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Eleonora
authors: E
authors: Giorgi
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Gian Nicola
authors: GN
authors: Gallus
authors: Department of Medical Biotechnologies, University of Siena, V. A. Moro, 2, 53100 Siena, Italy.
authors: Jlenia
authors: J
authors: Brunetti
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Carla
authors: C
authors: Battisti
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Alessandra
authors: A
authors: Rufa
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Maria Teresa
authors: MT
authors: Dotti
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy.
authors: Rossella
authors: R
authors: Franceschini
authors: Department of Medical Biotechnologies, University of Siena, V. A. Moro, 2, 53100 Siena, Italy.
authors: Luisa
authors: L
authors: Bracci
authors: Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100 Siena, Italy. Electronic address: federico@unisi.it.
authors: Antonio
authors: A
authors: Federico
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000097:blood* / Q000235:genetics*; D010375:Pedigree; D020033:Protein Isoforms
chemical_list: D020033:Protein Isoforms; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: 2-Deoxy-D-ribose (dRib); Apoptosis; Autosomal dominant optic atrophy (ADOA); Caspase 3; OPA1; Peripheral blood lymphocytes (PBLs)