Localization of survival motor neuron protein in human apoptotic-like and regenerating muscle fibers, and neuromuscular junctions.
Mutations in the gene encoding survival motor neuron (SMN) protein are found in > 98% of patients with autosomal-recessive spinal muscular atrophy. We investigated the possible role of SMN in normal and abnormal human muscle by immunostaining biopsies of 20 patients with various neuromuscular diseases using monoclonal antibodies against SMN. SMN was strongly expressed cytoplasmically in chronic peripheral neuropathies, in about 80% of chronically denervated, very atrophic muscle fibers containing clumps of TUNEL-positive pyknotic nuclei: about 60% of those fibers also had cytoplasmic Bcl-2 and Bax immunoreactivity. In regenerating muscle fibers of various myopathies SMN co-localized with desmin, Bcl-2 and Bax; it was also present at the postsynaptic domain of normal human neuromuscular junctions. Thus, SMN may play a role in normal and pathological processes of adult human muscle fibers.
Broccolini
A
A
USC Neuromuscular Center, Department of Neurology, University of Southern California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Engel
W K
WK
Askanas
V
V
D017209:Apoptosis; D017362:Cyclic AMP Response Element-Binding Protein; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009468:Neuromuscular Diseases / Q000473:pathology; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D012038:Regeneration; D055532:SMN Complex Proteins; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D051028:bcl-2-Associated X Protein