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Inclusion body myositis

Expression of extracellular signal-regulated kinase and its substrate

S. Nakano, MD, PhD;, A. Shinde, MD;, S. Kawashima, MD, PhD;, S. Nakamura, MD, PhD;, I. Akiguchi, MD, PhD; and J. Kimura, MD.

From the Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.



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  		Figure 1. Schematic diagram of the (A) extracellular signal-regulated kinase (ERK) pathway and the (B) stress-activated mitogen-activated protein kinase (MAPK) pathways. MEK = MAPK or ERK kinase; Elk-1 = the nuclear substrate of ERK; SRF = serum response factor; SRE = serum response element; MEKKs = MEK kinases; MKK3,6 = MAPK kinase; JNK = c-Jun N-terminal protein kinase; p38 = p38 MAPK; SEK-1 = SAPK/ERK kinase-1. For details, see references 10 and 12.

 


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  		Figure 2. Extracellular signal-regulated kinase immunostaining (A, C, E) in vacuolated fibers in inclusion body myositis, and nuclear DNA staining with Hoechst 33258 in the same sections (B, D, F). The bright spots represent nuclei (x680 before reduction).

 


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  		Figure 3. Elk-1 immunoreactivity (A, C, E) and nuclear staining (B, D, F) in the same sections in vacuolated fibers in inclusion body myositis (x680 before reduction).

 


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  		Figure 4. Two-color immunofluorescence. Localization in the same sections and fibers. Upper row: extracellular signal-regulated kinase (orange) and Elk-1 (green). Lower row: SMI-31 (orange) and Elk-1 (green) (x400).

 


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  		Figure 5. Extracellular signal-regulated kinase (ERK) and Elk-1 immunolocalization in control subjects. Positive deposits of (A) ERK and (B) Elk-1 in distal myopathy with rimmed vacuoles. (C) Small circular ERK-positive immunoreactivity in acid maltase deficiency. (D) ERK immunostaining in oculopharyngeal muscular dystrophy; only a small positive dot is observed in the vacuoles. (E) Cytoplasmic ERK-positive deposits in colchicine myopathy. (F) ERK-positive target formations in neurogenic muscular atrophy. (G) ERK and (H) Elk-1 in regenerating fibers in dermatomyositis. Elk-1 shows strong nuclear reactivity (x340 before reduction).

 




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