Search

To determine the relationship between myoglobin (Mb) and the defense system against reactive oxygen species in various myopathies, we performed immunohistochemical analyses of Mb and various antioxidant enzymes, including manganese superoxide dismutase (Mn-SOD), copper zinc SOD (CuZn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Biopsied muscle specimens were obtained from patients with chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), Duchenne muscular dystrophy (DMD), and polymyositis (PM). In patients with CPEO/KSS, stainings of Mb, SOD, CAT, and GSH-Px in nonatrophic ragged-red fibers (RRFs) were more intense than those in non-RRFs. These pronounced stainings corresponded to ragged-red lesions. The staining intensities of these antioxidant enzymes were significantly correlated with that of Mb (P < 0.001). Atrophic RRFs in specimens from patients with CPEO/KSS showed intense stainings of these antioxidant enzymes but not intense staining of Mb. In specimens from patients with DMD/PM, the antioxidant enzymes but not Mb were overexpressed in degenerative fibers. These results suggest that oxidative stress is associated with Mb expression specifically in mitochondrial diseases. The antioxidant enzymes seem to be upregulated to protect against muscle damage in nonatrophic RRFs. However, the Mb-mediated oxidative damage may become more extensive and result in further mitochondrial dysfunction and progressive atrophy of RRF with impaired upregulation of Mb.

The localization and amounts of myoglobin (Mb) and Mb mRNA in ragged-red fibers (RRF) in skeletal muscle of 6 patients with mitochondrial encephalomyopathy were examined immunohistochemically and by in situ hybridization. The amounts of Mb and Mb mRNA were expressed in terms of optical densities (ODs) of Mb immunostaining and Mb mRNA signals. In nonatrophic RRF, Mb was predominantly seen in the ragged-red region and Mb mRNA signals were increased throughout the sarcoplasm. The amounts of Mb and Mb mRNA in nonatrophic RRF were greater than those in nonatrophic non-RRF. In contrast, the localization and amount in atrophic RRF were similar to those in atrophic non-RRF. Thus, Mb synthesis in nonatrophic RRF may increase to compensate for mitochondrial dysfunction and to supply sufficient oxygen to mitochondria, but this compensatory function may be impaired in atrophic RRF.

Activities of nine lysosomal enzymes and pH-dependent isozyme patterns of α-mannosidase were examined in the skeletal muscle of patients with neuromuscular diseases, and the ratios of these enzyme activities in leukocytes to those in myocytes (UM ratio) were determined. The activities of enzymes with a high UM ratio were markedly increased in the muscles of patients with Duchenne muscular dystrophy (DMD), myotonic dystrophy (MyD), or polymyositis (PM). In contrast, those which showed a low UM ratio were increased in the muscles of amyotrophic lateral sclerosis (ALS) and disuse muscle atrophy (DUA). The isozyme pattern of α-mannosidase in DMD muscle resembled that in leukocytes, while those in ALS and DUA muscle resembled that in normal muscle. These results may suggest that the increased activity of lysosomal enzymes in the muscles of patients with DMD, MyD, or PM is due primarily to infiltrating leukocytes, while that in patients with ALS or DUA is due to intramyofiber lysosomes. 1995 John Wiley & Sons, Inc. . neuromuscular disease MUSCLE & NERVE 18 :1009-10151995

We report a Japanese family with chronic progressive external ophthal-moplegia (CPEO) with autosomal dominant inheritance, and review 54 reported CPEO patients in seven families (including the present family) with autosomal dominant inheritance and mtDNA deletions in the skeletal muscle. Mean age at onset in the CPEO was 26 years, which is older than that in published solitary cases. In addition to blepharoptosis and external ophthalmoplegia, proximal muscle atrophy and weakness were found in 62%, hearing loss in 25%, and ataxia in 17% of the patients. Retinal degeneration was not found, and cardiac involvement was very rare. mtDNA deletions in the muscle were multiple and large scale, and all such deletions were located in the non–D-loop region. Autosomal dominant CPEO has unique clinical features which differ from those of solitary CPEO, and is associated with multiple large-scale mtDNA deletions. Thus, autosomal dominant CPEO can be considered a clinical and genetic entity of mitochondrial diseases. © 1995 John Wiley & Sons, Inc.

Expression of the myoglobin (Mb) gene in skeletal muscle was studied in patients with Duchenne muscular dystrophy (DMD), polymyositis (PM), or amyotrophic lateral sclerosis (ALS) by measuring Mb concentration by radioimmunoassay and Mb messenger ribonucleic acid (RNA) (MbmRNA) levels by Northern blot analysis. Mb concentrations in the muscle cells (Mb/noncollagenous protein) were decreased in patients with DMD, PM, or ALS. However, while Mb concentrations per MbmRNA content (Mb/MbmRNA) were decreased in DMD and PM patients, these values were normal in ALS patients. These results suggest that Mb synthesis is increased in muscles of DMD and PM patients, but is not sufficient to compensate for the excessive loss of Mb from the affected muscles, and that the synthesis is decreased in the muscles of ALS patients. © 1994 John Wiley & Sons, Inc.

The localizations of myoglobin in skeletal muscle cells of patients with Duchenne muscular dystrophy (DMD), myotonic dystrophy (MyD), and amyotrophic lateral sclerosis (ALS) were studied by immunohistochemistry and immunoelectron microscopy. In normal skeletal muscle cells, myoglobin was localized mainly in the I-band region. In degenerating muscle cells of patients with DMD and MyD, myoglobin was also demonstrated in the distended lumen of the internal membrane system and in the intermyofibrillar space, through which it seemed to pass into the extracellular space. No myoglobin was detected in opaque fibers or in some of small-sized fibers in DMD muscle. In patients with ALS the staining intensities of myoglobin varied in different muscle cells, but myoglobin was restricted to the I-band region in many muscle cells. These findings suggest that changes in the localization of myoglobin in skeletal muscle cell sensitively reflect the pathologic status of muscle cells.

The localization of myoglobin in human skeletal muscle cell was studied by immunoelectron microscopy. The Fab'-horseradish peroxidase (HRP) conjugate was prepared by the maleimide method recently developed by Ishikawa et al. This method gave better recovery and less polymerization of HRP than the periodate method. By the direct immunoperoxidase method using this conjugate, myoglobin was shown to be localized in the I-band region of skeletal muscle cells. The outer membrane of mitochondria and triads stained intensely, but A-bands were not stained. Myonuclei and intermyofibrillar spaces were also not stained. The localization of myoglobin in the I-band implies its function in energy generation.