| Project/Area Number |
18590960
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
NAKANO Satoshi Kansai Medical University, Neurology, Assistant Professor (30333206)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHINDE Akiyo Kansai Medical University, Neurology, Instructor (10368235)
ITO Hidefumi Kansai Medical University, Neurology, Associate Professor (20250061)
KUSAKA Hirofumi Kansai Medical University, Neurology, Professor (70250066)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,320,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | Neurology / Myopathy / Pathology / DNA double-strand breaks |
|---|
| Research Abstract |
Objectives: To examine DNA damage response in s-IBM. Background: In sporadic inclusion body myositis, several studies have indicated that myonuclear abnormality may be closely associated with its pathogenesis. Materials & Methods: Immunhistochemistry in biopsy materials from patients with s-IBM (n=17), polymyositis (15), dermatomyositis (10) and other controls (10). Antibodies against 1) phosphorylated histone H2AX (γH2AX) that accumulates to the damaged sites with DNA double-strand breaks (DSB); and 2) DNA-PK that is an enzyme involved in DSB repair. DNA-PK consists of a catalytic subunit (DNA-PKcs) and regulatory subunits (Ku70 and Ku80). Results: In s-IBM and other myositis controls, a proportion of myonuclei showed strong immunoreactivity of γH2AX and DNA-PK while normal controls showed weak myonuclear reactivity. In muscle fibers with vacuoles in s-IBM, vacuolar rims were frequently positive for γH2AX and DNA-PK. Whereas DNA-PKcs and Ku80 were associated with DNA in vacuolated fibers, Ku70 was observed in the cytoplasm as inclusions. Conclusions: DSB occurs in some myonuclei in inflammatory myopathies. In s-IBM, the cytoplasmic accumulation of Ku70 regulatory component of DNA-PK may prevent their translocation to the nucleus and DSB sites. Accumulation of DSB may lead to the myonuclear degeneration in s-IBM.
|
