Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis

Nakano, Satoshi; Shinde, Akiyo; Fujita, Kazuko; Ito, Hidefumi; Kusaka, Hirofumi

doi:10.1016/j.nmd.2007.08.005

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…In that study, 73% of H&E-rimmed vacuoles corresponded with emerin-lined vacuoles on serial sections of muscle. Subsequent papers have identifi ed valosin-containing protein as a myonuclear protein and a component of some IBM-rimmed vacuoles [40], which were not quantitated, and identifi ed the presence of nuclear protein histone H1 lining about 60% of vacuoles [41]. This latter study confi rmed the previously reported presence of emerin [39•].…”

Section: Nuclear Degenerationsupporting

confidence: 65%

Inclusion body myositis: Review of recent literature

Greenberg

2008

Curr Neurol Neurosci Rep

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Inclusion body myositis (IBM) is a progressive inflammatory skeletal muscle disease of unknown cause and without effective treatment. This article discusses existing literature, emphasizing disease mechanisms and models. In particular, it addresses limitations in the beta-amyloid-mediated theory of IBM myofiber injury, flawed rationales of animal models of this disease, and recent reports regarding treatment.

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Section: Nuclear Degenerationsupporting

confidence: 65%

Inclusion body myositis: Review of recent literature

Greenberg

2008

Curr Neurol Neurosci Rep

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“…Immunohistochemical evidence that rimmed vacuoles are lined with the nuclear membrane proteins lamin A/C and emerin was reported in 2006 [43]. Lining of these vacuoles with histone H1 and with emerin was reported in 2008 [52] and with histone 2AX and DNA repair regulatory components (DNA-dependent protein kinase, Hu70, and Hu80) in 2011 [53 & ]. Whether this nuclear degeneration relates to TDP-43 accumulation in sarcoplasm is not known.…”

Section: Nuclear Degenerationmentioning

confidence: 99%

Pathogenesis and therapy of inclusion body myositis

Greenberg

2012

Current Opinion in Neurology

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“…Many of the myonuclei are enlarged, contain eosinophilic inclusions or are located within the vacuoles and appear to be exploding into the vacuoles themselves. Interestingly, the rimmed vacuoles immunostain with antibodies directed against the nuclear proteins such as emerin, lamin A/C, valosin containing protein (VCP), histone and 43 kDa TAR DNA binding protein, suggesting a component of the rimmed vacuoles may be secondary to remnants of destroyed myonuclei41 42 43 44 45 Various “Alzheimer characteristic proteins” are also evident by immunohistochemistry, mainly in vacuolated muscle fibres, but the significance is unclear (see pathogenesis section).…”

Section: Histopathologymentioning

confidence: 99%

“…It is interesting in regard to oculopharyngeal muscular dystrophy and Emery–Dreifuss muscular dystrophy that the mutated proteins localise to nuclei. Given the rimmed vacuoles immunostain with antibodies directed against the nuclear proteins such as emerin, lamin A/C, VCP and histone 1 and that myonuclei often are abnormal and filled with neurofilaments on EM, we would speculated that myonuclear degeneration is probably one of the earliest features of the disease and must be directly related to the pathogenesis 41 42 43 44 59…”

Section: Pathogenesismentioning

confidence: 99%

Inclusion body myositis: old and new concepts

Amato

Barohn

2009

Journal of Neurology, Neurosurgery & Psychiatry

104

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Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy occurring in patients over the age of 50 years and probably accounts for about 30% of all inflammatory myopathies. Muscle biopsy characteristically reveals endomysial inflammation, small groups of atrophic fibres, eosinophilic cytoplasmic inclusions and muscle fibres with one or more rimmed vacuoles. However, any given biopsy may lack these histopathological abnormalities; the clinical examination is often the key to diagnosis. Early and often asymmetrical weakness and atrophy of the quadriceps and flexor forearm muscles (ie, wrist and finger flexors) are the clinical hallmarks of IBM. The pathogenesis of IBM is unknown. It may be autoimmune inflammatory myopathy or a primary degenerative myopathy with a secondary inflammatory. A prevailing theory is that there is an overproduction of beta-amyloid precursor protein in muscle fibres that is somehow cleaved into abnormal beta-amyloid, and the accumulation of the latter is somehow toxic to muscle fibres. However, there are many problems with this theory and more work needs to be done. Unfortunately, IBM is generally refractory to therapy. Further research into the pathogenesis, along with both preliminary small pilot trials and larger double blind, placebo controlled efficacy trials, are needed to make progress in our understanding and therapeutic approach for this disorder.

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Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis

Cited by 24 publications

References 27 publications

Inclusion body myositis: Review of recent literature

Inclusion body myositis: Review of recent literature

Pathogenesis and therapy of inclusion body myositis

Inclusion body myositis: old and new concepts

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