Reduced Aquaporin 4 Expression in the Muscle Plasma Membrane of Patients With Duchenne Muscular Dystrophy

Wakayama, Yoshihiro; Jimi, Takahiro; Inoue, Masahiko; Kojima, Hiroko; Murahashi, Makoto; Kumagai, Toshiyuki; Yamashita, Sumimasa; Hara, Hajime; Shibuya, Seiji

doi:10.1001/archneur.59.3.431

Cited by 58 publications

(46 citation statements)

References 29 publications

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“…These antisera were affinity purified. The affinity purified rabbit polyclonal AQP4 antibody against the C-terminal end of the rat AQP4 was also previously produced in our laboratory [18].…”

Section: Peptide Synthesis and Antibody Productionmentioning

confidence: 99%

“…F0205, Denmark) diluted 1:50 in PBS for 60 min at room temperature. For the judgment of myofiber type [19], serial sections of HE or oil red O stained muscle samples and the immunostained muscle samples with anti-AQP7 or AQP9 antibody from obese DIO or control chow-fed mice were also immunostained with the affinity purified rabbit anti-AQP4 antibody at the IgG concentration of 5 µg/ml [18]. The immunostained muscles were examined using Nikon H 550L fluorescent microscope.…”

Section: Histopathological and Immunohistochemical Studiesmentioning

confidence: 99%

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AQP7 Up-Regulation in the Skeletal Muscles of Mice with Diet Induced Obesity

Wakayama¹

2015

J Cell Sci Ther

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Aquaporin (AQP) 7 and AQP9 are membrane proteins and are the members of aquaglyceroporin which transports glycerol in addition to water molecule. Glycerol is a direct source of glycerol-3 phosphate for the synthesis of triglycerides. We thought that the expression of AQP7 and AQP9 would be altered in the skeletal myofibers in mice with diet-induced obesity (DIO) as compared with that of control chaw-fed mice. RNA and protein levels of AQP7 and AQP9 were studied in the quadriceps femoris muscles of mice with DIO and normal control mice. Real time quantitative RT-PCR analysis showed that mouse AQP7 mRNA levels in skeletal muscles were significantly higher in mice with DIO than in normal control mice (P<0.01); whereas mouse AQP9 mRNA levels were not different between the two groups (P>0.05). Histochemically the myofibers of mice with DIO contained numerous lipid droplets in oil red O stain samples. Immunohistochemical study of DIO mouse muscles showed enhanced expression of AQP7 at the myofiber surface membranes; while AQP9 expression appeared to be similar to that of normal control mice. These findings imply that the up-regulated expression of AQP7 in DIO mouse muscles facilitates the secretion of glycerol from myocytes.

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Section: Peptide Synthesis and Antibody Productionmentioning

confidence: 99%

Section: Histopathological and Immunohistochemical Studiesmentioning

confidence: 99%

AQP7 Up-Regulation in the Skeletal Muscles of Mice with Diet Induced Obesity

Wakayama¹

2015

J Cell Sci Ther

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“…Vajda et al (2002) also showed the delayed onset of brain edema in dystrophin-null transgenic mice. In muscular dystrophy, reduced AQP4 expression was found in skeletal muscle plasma membrane (Crosbie et al 2002;Frigeri et al 2002;Wakayama et al 2002). Frigeri et al (2001) reported that the AQP4 mRNA content of mdx mouse muscles and brains was qualitatively the same as that of mdx control mouse muscles and brains, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that the OAs were severely reduced and the anti-AQP4 antibody immunoreactivity was markedly reduced in these muscle plasma membranes. We reported that the severely decreased AQP4 expression of DMD muscles was due to the decreased AQP4 mRNA content of DMD muscles (Wakayama et al 2002). We thought whether the decreased AQP4 expression of mdx mice was due to the same mechanism as described in DMD muscles, and were interested in the measurement of the AQP4 mRNA content of mdx mouse muscles.…”

Section: Real-time Quantitative Reverse Transcription Polymerase Chaimentioning

confidence: 99%

“…Following this discovery, the mercury-insensitive water channel AQP4 has been most intensively studied so far in skeletal muscle (Wakayama et al 2007). Previously we investigated the muscle plasma membrane of boys with Duchenne muscular dystrophy (DMD) and dystrophin-deficient mdx mouse by the freeze fracture electron microscopy (Schotland et al 1981;Wakayama et al 1984;Shibuya and Wakayama 1988) and by the anti-AQP4 antibody immunohistochemistry (Crosbie et al 2002;Frigeri et al 2002;Wakayama et al 2002). The results showed that the OAs were severely reduced and the anti-AQP4 antibody immunoreactivity was markedly reduced in these muscle plasma membranes.…”

Section: Real-time Quantitative Reverse Transcription Polymerase Chaimentioning

confidence: 99%

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Aquaporin 4 mRNA Levels in Neuromuscular Tissues of Wild-type and Dystrophin-deficient Mice

Shibuya

Hara

Wakayama

et al. 2008

Tohoku J. Exp. Med.

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Aquaporin (AQP) 4 is a water-specific channel protein and is abundant in central nervous tissues and skeletal muscles. Recently, the AQP4 molecule has been increasingly highlighted in its pathophysiological role of several neurological diseases, such as stroke, muscular dystrophy and neuromyelitis optica. We therefore measured the levels of AQP4 mRNA and glyceraldehyde-3 phosphate dehydrogenase mRNA (an internal control) in muscle and brain tissues of wild-type mice (C57BL10/ScSn) and age-matched dystrophindeficient mdx mice (C57BL10/ScSn mdx) by real-time quantitative RT-PCR. The relative AQP4 mRNA level was highest in the spinal cord among the neuromuscular tissues examined in wild-type mice. Among the muscle tissues of wild-type mice, the relative AQP4 mRNA level was higher in extensor digitorum longus (EDL) muscles, and its descending order was EDL, quadriceps femoris, soleus and heart muscles. It is noteworthy that there was no difference in the relative AQP4 mRNA levels in the brain tissues between wildtype mice and age-matched mdx mice. In contrast, the AQP4 mRNA level in the quadriceps femoris muscle was significantly lower in mdx mice than in wild-type mice. The fact that the spinal cord contains the highest AQP4 mRNA may be related to the pathogenesis of neuromyelitis optica, in which AQP4 protein is the target antigen. In addition, the low expression level of AQP4 mRNA in the mdx mouse muscle suggests a functional link between AQP4 and dystrophin in the muscle tissue. We suggest that a similar pathomechanism may underlie the phenotypic consequences of the mdx mouse and Duchenne muscular dystrophy. The water molecule is essential for the living organism. Aquaporins (AQPs) comprise a large family of integral membrane proteins that form a water channel in animals, plants and microorganisms. They play a role in bidirectional water movement in response to osmotic gradients created by ion pumping and are expressed widely in mammalian epithelia and endothelia. In skeletal muscle cells (Rash and Ellisman 1974) and brain astrocytes (Landis and Reese 1981), the freeze fracture electron microscopy revealed the presence of many orthogonal arrays (OAs) which are identified as aggregates of 4 or more 6-nm diameter particles in the P face and as aggregates of 4 or

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Autoimmune Aquaporin-4 Myopathy in Neuromyelitis Optica Spectrum

et al. 2014

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We report on a 51-year-old woman who had relapsing optic neuritis, transverse myelitis, AQP4-IgG seropositivity, and recurrent myalgias with hyperCKemia. A muscle biopsy revealed scattered myofibers with internal nuclei, atrophy, and regeneration but no necrosis. Mild inflammatory exudates, in endomysial and perivascular spaces, consisted of lymphocytes, histiocytes, and scattered eosinophils. The sarcolemma exhibited loss of AQP4 and deposition of IgG and complement activation products, characteristics not seen in control biopsy samples of healthy muscle and immune-mediated myopathies.CONCLUSIONS AND RELEVANCE Recurrent hyperCKemia accompanying AQP4-IgG seropositivity reflects targeting of skeletal muscle AQP4 by pathogenic IgG. The entity of autoimmune AQP4 myopathy extends the neuromyelitis optica spectrum beyond the central nervous system.

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Reduced Aquaporin 4 Expression in the Muscle Plasma Membrane of Patients With Duchenne Muscular Dystrophy

Abstract: The reduction in AQP4 in DMD muscles results from decreased levels of AQP4 mRNA in DMD myofibers.

Cited by 58 publications

References 29 publications

AQP7 Up-Regulation in the Skeletal Muscles of Mice with Diet Induced Obesity

AQP7 Up-Regulation in the Skeletal Muscles of Mice with Diet Induced Obesity

Aquaporin 4 mRNA Levels in Neuromuscular Tissues of Wild-type and Dystrophin-deficient Mice

Autoimmune Aquaporin-4 Myopathy in Neuromyelitis Optica Spectrum

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