title: Apoptosis and ROS detoxification enzymes correlate with cytochrome c oxidase deficiency in mitochondrial encephalomyopathies.
abstract: The aim of this work was to investigate in muscle the role of apoptosis and of oxidative stress in mitochondrial disorders with dysfunction of respiratory chain. In patients with cytochrome c oxidase deficiency (COX) we found a variable number of myofibers with apoptotic nuclei that matched with the level of enzymatic reduction and roughly correlated with muscle weakness. In parallel, a positive immunostaining for apoptosis-related proteins and Mn and Cu/Zn superoxide dismutase (SOD) were mostly localized in COX-negative fibers. Moreover, glutathione peroxidase activity was increased in muscles with high number of SOD-positive myofibers and prominent apoptotic features. No signs of apoptosis were observed in patients with deficiencies of complexes I and II and without muscle weakness. These data suggest that apoptosis along with increased ROS production, revealed by anti-oxidant enzymes overexpression, may play an important role in the pathophysiology of mitochondrial diseases associated with COX deficiency.
authors: Institute of Neurology, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy.
authors: S
authors: S
authors: Di Giovanni
authors: M
authors: M
authors: Mirabella
authors: M
authors: M
authors: Papacci
authors: F
authors: F
authors: Odoardi
authors: G
authors: G
authors: Silvestri
authors: S
authors: S
authors: Servidei
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001706:Biopsy; D020170:Caspase 1 / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D053938:DNA Fragmentation; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology* / Q000473:pathology*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D019014:fas Receptor; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1