Antioxidant agents have a different expression pattern in muscle fibers of patients with mitochondrial diseases

• Published in: Acta neuropathologica 2002-03, Vol.103 (3), p.215-220
• Main Authors: FILOSTO, Massimiliano, TONIN, Paola, VATTEMI, Gaetano, SPAGNOLO, Michele, RIZZUTO, Nicolo, TOMELLERI, Giuliano
• Format: Article
• Language: English
• Subjects: Acidosis; Adult; Aged; Aged, 80 and over; Antioxidants; Antioxidants - metabolism; Biological and medical sciences; Biopsy; Cytoplasm; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease; DNA, Mitochondrial - genetics; DNA, Mitochondrial - immunology; DNA, Mitochondrial - metabolism; Enzymes; Epilepsy; Female; Free Radical Scavengers - immunology; Free Radical Scavengers - metabolism; Gene Expression - genetics; Gene Expression - immunology; Genotype & phenotype; Glutathione - genetics; Glutathione - immunology; Glutathione - metabolism; Histology; Humans; Hydrogen peroxide; Male; Medical sciences; Middle Aged; Mitochondrial Diseases - genetics; Mitochondrial Diseases - immunology; Mitochondrial Diseases - metabolism; Mitochondrial DNA; Muscle Fibers, Skeletal - immunology; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - immunology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Musculoskeletal system; Mutation; Neurology; Oxidative stress; Patients; Stains & staining; Superoxide Dismutase - genetics; Superoxide Dismutase - immunology; Superoxide Dismutase - metabolism
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010100455

Respiratory chain dysfunction leads to reactive oxygen species (ROS) generation with following oxidative stress and cellular damage. A histochemical and immunohistochemical study was performed on muscle biopsies from 17 patients with mitochondrial disease [chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF)] to evaluate the expression pattern and location of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and reduced glutathione (GSH) in skeletal muscle fibers. Our data showed that: (1) MnSOD, CuZnSOD and GSH are expressed in fibers with respiratory chain deficiency; (2) the antioxidant induction is correlated with the degree of mitochondrial proliferation, but not with clinical phenotype, patients' age, duration of disease, biochemical defects or mitochondrial DNA abnormalities. In addition, we suggest that expression of MnSOD and GSH may be considered an initial, indirect sign of respiratory chain dysfunction because it is observed in the early stages of the disease.