Localization of O-GlcNAc-modified proteins in neuromuscular diseases.
O-linked N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of nucleocytoplasmic proteins that induces the attachment of N-acetylglucosamine to serine or threonine residues of a protein. In contrast to other protein glycosylations, this modification is highly reversible and, similar to phosphorylation, it plays important roles in various cell signals. Here, we immunolocalized O-GlcNAc-modified proteins in muscle biopsy specimens from 40 patients with neuromuscular diseases and controls. In normal muscle fibers, O-GlcNAc was found along plasma membranes and in nuclei. Diffuse and increased cytoplasmic staining of O-GlcNAc was detected in (1) regenerating muscle fibers in muscular dystrophy, myositis, and rhabdomyolysis; (2) a proportion of atrophic fibers in myositis, such as those found in perifascicular regions in dermatomyositis; and (3) vacuolated fibers in sporadic inclusion body myositis (s-IBM) and distal myopathy with rimmed vacuoles (DMRV). Target formations in neurogenic muscular atrophy were O-GlcNAc positive. Increase of O-GlcNAc glycosylation could be associated with the stress response, as these lesions have been shown to be positive for several stress markers. Vacuolar rims in s-IBM and DMRV were sometimes sharply lined by O-GlcNAc-positive deposits, which reflects myonuclear breakdown occurring from the disease.
Department of Neurology and Brain Medical Research Center, Kansai Medical University, Osaka, Japan.
Seika
S
Nakamura
Satoshi
S
Nakano
Makoto
M
Nishii
Satoshi
S
Kaneko
Hirofumi
H
Kusaka
D000117:Acetylglucosamine / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006031:Glycosylation; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000378:metabolism / Q000473:pathology; D009468:Neuromuscular Diseases / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D012206:Rhabdomyolysis / Q000378:metabolism / Q000473:pathology
D050884:HSP72 Heat-Shock Proteins; D011506:Proteins; D000117:Acetylglucosamine