The muscle mitogen-activated protein kinase is altered in sporadic inclusion body myositis.
Neurology
; 54(8): 1665-70, 2000 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-10762511
ABSTRACT
OBJECTIVE:
To examine the origin of hyperphosphorylated proteins within the vacuolated myofibers in sporadic inclusion body myositis (s-IBM) and search for dysregulated intracellular protein phosphorylation.BACKGROUND:
s-IBM is morphologically characterized by primary endomysial inflammation and vacuolated myofibers containing tubulofilaments that originate from cytoskeletal proteins. Mitogen-activated protein kinases (MAPKs) play a role in regulating phosphorylation and maintaining the stability of the cytoskeletal architecture.METHODS:
Muscle biopsies from seven patients with s-IBM and 15 controls were examined for the expression of the active components of the various MAPKs, including p44/42MAPK, p38MAPK, p46JNK1, p54JNK2, and p54JNK3, using immunocytochemistry and Western blot analysis. The expression of selected phosphorylated components was also examined in the same specimens.RESULTS:
In s-IBM, but not the disease controls, the vacuolated muscle fibers express active p42MAPK but not JNK or p38MAPK. Western blots of cell lysates confirmed the hyperexpression of p42MAPK and demonstrated a novel 35 kD phosphoprotein. Antibodies against phosphoepitopes of the 35 kD protein preferentially immunostained antigens within the vacuolated muscle fibers of s-IBM but not disease controls.CONCLUSION:
In s-IBM, there is increased p42MAPK activation and abnormal intracellular protein phosphorylation with selective accumulation of a 35 kD phosphoprotein within the vacuolated fibers. Although the hyperexpression of 35kD protein may represent cytoskeletal by-products due to heightened p42MAPK activation, its abundant expression only in s-IBM implies that hyperphosphorylated myofibrillar proteins may be involved in the primary disease process.
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Banco de datos:
MEDLINE
Asunto principal:
Músculo Esquelético
/
Miositis por Cuerpos de Inclusión
/
Proteínas Quinasas Activadas por Mitógenos
Tipo de estudio:
Clinical_trials
Límite:
Aged
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
Neurology
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos