2002 Fiscal Year Final Research Report Summary
Muscular Dystrophy and Nitric Oxide
| Project/Area Number |
12670151
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY |
|---|
Principal Investigator |
YOSHIDA Mikiharu Natl. Inst. Neurosci, NCNP; Section Chief, 神経研究所, 室長 (70111151)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | muscular dystrophy / α-dystrobrevin / neuronal nitric oxide synthase / sarcoglycan complex / syntrophin / dystrophin-associated protein |
|---|
| Research Abstract |
We started this study assuming the regulation of the neuronal nitric oxide synthase (nNOS) activity by the transmembranous sarcoglycan complex through the cytoskeletal protein α-dystrobrevin (DB), based on our finding of a direct binding between the sarcoglycan complex and DB present in the oligomeric complex composed of dystrophin and the dystrophin-associated proteins (DAPs). This is because DB is also associated with syntrophin that is known as an anchor protein for nNOS. DB-3, the shortest isoform among the DBs expressed in skeletal muscle, is unique because it lacks binding sites for both dystrophin and syntrophin.
Using an antibody against DB-3, we demonstrated that DB-3 is expressed as one of the DAPs. Moreover, immunoprecipitation study showed that each DB isoform forms a distinct dystrophin-DAP complex, and that the syntrophins only in the complex containing DB-3 are markedly reduced, despite the presence of syntrophin- binding sites on dystrophin. This finding indicates that stable binding of syntrophin to the dystrophin-DAP complex requires binding sites for it on both dystrophin and DB. This finding also suggests that there exists in vivo the dystrophin-DAP complex that is not associated with nNOS. We have immunohistochemically examine the distribution of DBs on the costameric structure present on the sarcolemma. Also we have biochemically examine the DBs in the caveolin-3-associated membrane raft fraction. This is because caveolin-3 is known to bind with dystrophin through nNOS. However, we have not yet obtained the conclusive results, partially because of our technical problems.
|
Research Products
(10 results)
-
-
-
-
-
-
-
[Publications] Sasaoka T, Imamura M, Araishi K, Noguchi S, Mizuno Y, Takagoshi N, Hama H, Wakabayashi-Takai E, Yoshimoto-Matsuda Y, Nonaka I, Kaneko K, Yoshida M & Ozawa E: "Pathological analysis of muscle hypertrophy and degeneration in muscular dystrophy in gamma-sarcoglycan-deficient mice"Neuromuscul Disord. 13-3. 193-206 (2003)
Description
「研究成果報告書概要(欧文)」より
-
-
-
