Caveolin-3 deficiency causes muscle degeneration in mice

Hagiwara, Yasuko; Sasaoka, Toshikuni; Araishi, Kenji; Imamura, Michihiro; Yorifuji, Hiroshi; Nonaka, Ikuya; Ozawa, Eijiro; Kikuchi, Tateki

doi:10.1093/hmg/9.20.3047

Cited by 154 publications

(130 citation statements)

References 33 publications

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“…As it penetrates, EBD stains only damaged muscle fibers and is useful for evaluating the extent of muscle fiber degeneration. 28,35 After isolation, the diaphragms were rinsed in PBS, fixed in 10% formalin, and evaluated macroscopically.…”

Section: Systemic Treatment With Mg-132mentioning

confidence: 99%

Proteasome Inhibitor (MG-132) Treatment of mdx Mice Rescues the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins

Bonuccelli

Sotgia

Schubert

et al. 2003

The American Journal of Pathology

112

110

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Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is absent in the skeletal muscle of DMD patients and mdx mice. At the plasma membrane of skeletal muscle fibers, dystrophin associates with a multimeric protein complex, termed the dystrophin-glycoprotein complex (DGC). Protein members of this complex are normally absent or greatly reduced in dystrophin-deficient skeletal muscle fibers, and are thought to undergo degradation through an unknown pathway. As such, we reasoned that inhibition of the proteasomal degradation pathway might rescue the expression and subcellular localization of dystrophin-associated proteins. To test this hypothesis, we treated mdx mice with the wellcharacterized proteasomal inhibitor MG-132. First, we locally injected MG-132 into the gastrocnemius muscle, and observed the outcome after 24 hours. Next, we performed systemic treatment using an osmotic pump that allowed us to deliver different concentrations of the proteasomal inhibitor, over an 8-day period. By immunofluorescence and Western blot analysis, we show that administration of the proteasomal inhibitor MG-132 effectively rescues the expression levels and plasma membrane localization of dystrophin, ␤-dystroglycan, ␣-dystroglycan, and ␣-sarcoglycan in skeletal muscle fibers from mdx mice. Furthermore, we show that systemic treatment with the proteasomal inhibitor 1) reduces muscle membrane damage, as revealed by vital staining (with Evans blue dye) of the diaphragm and gastrocnemius muscle isolated from treated mdx mice, and 2) ameliorates the histopathological signs of muscular dystrophy, as judged by hematoxylin and eosin staining of muscle biopsies taken from treated mdx mice. Duchenne muscular dystrophy (DMD) is one of the most prevalent and severe inherited diseases of childhood, characterized by progressive muscular wasting and weakness. The deficient gene product, dystrophin, 1 is a peripheral membrane protein of ϳ426 kd, which is expressed in muscle tissues and the brain. At the plasma membrane, dystrophin associates with a large multimeric complex, termed the dystrophin-glycoprotein complex (DGC). 2 The DGC is composed of two subcomplexes: the dystroglycan complex (␣ and ␤ subunits) and the sarcoglycan complex (␣, ␤, ␥, and ␦ subunits). The Nterminal region of dystrophin interacts directly with the cytoskeletal protein actin, while the dystrophin C-terminal domain binds to the plasma membrane through interactions with ␤-dystroglycan. As such, dystrophin is thought

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Section: Systemic Treatment With Mg-132mentioning

confidence: 99%

Proteasome Inhibitor (MG-132) Treatment of mdx Mice Rescues the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins

Bonuccelli

Sotgia

Schubert

et al. 2003

The American Journal of Pathology

112

110

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“…In contrast to caveolin-1 and -2 which are most abundantly expressed in adipocytes, endothelial cells and fibroblastic cell types, caveolin-3 expression is mostly confined to striated (cardiac and skeletal) and smooth muscle. Caveolin-3 in muscle cells has been shown to be responsible for organelle biogenesis in these tissues and caveolin-3 null mice lack caveolae only in these tissues (Hagiwara et al, 2000;Galbiati et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in H9c2 cardiomyoblasts

Pak²

2005

Exp Mol Med

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“…However, because some apparent mutations of caveolin-3 gene have turned out to be harmless, the problem is raised whether deficiency of caveolin-3 causes dystrophic phenotypes or not. Recently, we developed caveolin-3-null mice that have a mild muscular dystrophic phenotype, although the disease is inherited in an autosomal recessive manner (Hagiwara et al, 2000). This was followed by a similar report (Galbiati et al, 2001).…”

mentioning

confidence: 98%

Immunolocalization of Caveolin-1 and Caveolin-3 in Monkey Skeletal, Cardiac and Uterine Smooth Muscles.

Hagiwara

Nishina

Yorifuji

et al. 2002

Cell Struct. Funct.

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ABSTRACT. Caveolin, a 20-24 kDa integral membrane protein, is a principal component of caveolar domains. Caveolin-1 is expressed predominantly in endothelial cells, fibroblasts, and adipocytes, while the expression of caveolin-3 is confined to muscle cells. However, their localization in various muscles has not been well documented. Using double-immunofluorescence labeling and confocal laser microscopy, we examined the localization of caveolins-1 and 3 in adult monkey skeletal, cardiac and uterine smooth muscles and the co-immunolocalization of these caveolins with dystrophin, which is a product of the Duchenne muscular dystrophy gene. In the skeletal muscle tissue, caveolin-3 was localized along the sarcolemma except for the transverse tubules, and coimmunolocalized with dystrophin, whereas caveolin-1 was absent except in the blood vessels of the muscle tissue. In cardiac muscle cells, caveolins-1 and -3 and dystrophin were co-immunolocalized on the sarcolemma and transverse tubules. In uterine smooth muscle cells, caveolin-1, but not caveolin-3, was co-immunolocalized with dystrophin on the sarcolemma.

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Caveolin-3 deficiency causes muscle degeneration in mice

Cited by 154 publications

References 33 publications

Proteasome Inhibitor (MG-132) Treatment of mdx Mice Rescues the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins

Proteasome Inhibitor (MG-132) Treatment of mdx Mice Rescues the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins

Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in H9c2 cardiomyoblasts

Immunolocalization of Caveolin-1 and Caveolin-3 in Monkey Skeletal, Cardiac and Uterine Smooth Muscles.

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