Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis.
To investigate myonuclear alterations in sporadic inclusion body myositis (s-IBM), we immuno-localized histones in muscles in 11 patients. The examination showed that vacuolar rims were frequently positive for histone H1. In triple-color fluorescence study, the H1-positive products were found on the inner side of an emerin-positive circle with DNA. Moreover, H1-positive materials appeared to be released into the cytoplasm in some vacuoles and myonuclei. The localization of H1 was different from phosphorylated Elk-1, which is a nuclear protein, but abnormally accumulated in the cytoplasm in s-IBM. The results strongly support the hypothesis that rimmed vacuoles are derived from the nucleus. The cytoplasmic H1-release suggests dysfunction of nuclear membranes in an early phase of the nuclear disintegration. We hypothesize that, in s-IBM muscles, compromised nuclear envelope may permit release of some nuclear components such as histone H1 and cannot facilitate the incorporation of others to the nucleus as in pElk-1.
Nakano
Satoshi
S
Department of Neurology, Kansai Medical University, Moriguchi 570-8507, Japan. nakanos@takii.kmu.ac.jp
Shinde
Akiyo
A
Fujita
Kengo
K
Ito
Hidefumi
H
Kusaka
Hirofumi
H
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009685:Nuclear Envelope / Q000378:metabolism / Q000473:pathology; D014617:Vacuoles / Q000378:metabolism* / Q000473:pathology; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
D006657:Histones; D050807:ets-Domain Protein Elk-1; D004247:DNA