Abstract
Abnormalities of the sarcotubular system presenting as tubular aggregates (TAs) have been described in a variety of neuromuscular disorders. Here, we report on immunohistochemical and biochemical findings in 7 patients (2 familial and 5 sporadic cases) suffering from myopathies with TAs. In muscle biopsy specimens from 5 of the 7 patients, TAs were immunopositive for the ryanodine receptor (RYR 1) of the sarcoplasmic reticulum (SR), the SR Ca2+ pump (SERCA2-ATPase), and the intraluminal SR Ca2+ binding protein calsequestrin, indicating an SR origin of these aggregates. Furthermore, these 5 cases showed decreased respiratory chain enzyme activities (NADH:CoQ oxidoreductase. complex I and cytochrome c oxidase [COX], complex IV), while the remaining 2 patients exhibited normal values. Our findings indicate a functional link between mitochondrial dysfunction and the presence of TAs originating from the sarcoplasmic reticulum.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Biopsy
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Calcium-Transporting ATPases / analysis
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Calcium-Transporting ATPases / immunology
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Calsequestrin / analysis
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Calsequestrin / immunology
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Cell Respiration
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DNA, Mitochondrial / analysis
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Energy Metabolism
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Humans
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Immunohistochemistry
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Male
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Microscopy, Electron
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Middle Aged
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Mitochondrial Myopathies / metabolism*
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Mitochondrial Myopathies / pathology*
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Muscle Fibers, Skeletal / chemistry
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Muscle Fibers, Skeletal / enzymology
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Muscle Fibers, Skeletal / ultrastructure
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Muscle, Skeletal / chemistry
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Oxidative Phosphorylation
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Ryanodine Receptor Calcium Release Channel / analysis
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Ryanodine Receptor Calcium Release Channel / immunology
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Saponins
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Sarcoplasmic Reticulum / metabolism*
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Sarcoplasmic Reticulum / pathology*
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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Titrimetry
Substances
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Calsequestrin
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DNA, Mitochondrial
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Ryanodine Receptor Calcium Release Channel
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Saponins
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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ATP2A2 protein, human
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Calcium-Transporting ATPases