Résumé :
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Although several reports indicate that dystrophic muscle exhibits elevated nuclear p65 activation, little is known regarding the disposition of the alternative pathway in dystrophic muscle. In nondystrophic muscle, several of the components of the alternative NF?B signaling pathway are upregulated by disuse and this upregulation is associated with a reduction in the expression of pro-apoptotic proteins and an increase in expression of anti-apoptotic proteins (Hunter et al., FASEB J., 16, 529-538, 2002). To examine the potential role of the alternative NF?B pathway in muscular dystrophy, cytosolic, nuclear, and whole cell extracts from adult nondystrophic and mdx costal diaphragms were used to examine the expression of NF?B signaling components along the alternative pathway. Whole cell extracts obtained from mdx costal diaphragm exhibited significantly increased expression of rel B, p 52, and p100 (Western blot densitometric analysis with GAPDH as loading control) in comparison to nondystrophic diaphragm. The ratio of p52/p100 which represents the activity of the proteasome in degrading p100 was also significantly increased in dystrophic muscle. These increases were associated with corresponding increases in the expression of IKK? and in the phosphorylation of NIK (Pi NIK/total NIK). These results provide evidence that both the classical and alternative NF?B pathways exhibit elevated signaling in adult dystrophic skeletal muscle, and indicate a need for additional studies to identify whether the alternative pathway is compensatory or detrimental to the structure and function of dystrophic skeletal muscle. (Supported by AFM, Charley’s Fund, Strategic Research Grant from ATSU)
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