Apoptosis and ROS detoxification enzymes correlate with cytochrome c oxidase deficiency in mitochondrial encephalomyopathies.
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.
Di Giovanni
S
S
Institute of Neurology, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy.
Mirabella
M
M
Papacci
M
M
Odoardi
F
F
Silvestri
G
G
Servidei
S
S
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
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