Anti-interleukin-6 receptor antibody prevents muscle atrophy in colon-26 adenocarcinoma-bearing mice with modulation of lysosomal and ATP-ubiquitin-dependent proteolytic pathways
✍ Scribed by Junya Fujita; Toshimasa Tsujinaka; Masahiko Jano; Chikara Ebisui; Hiroyuki Saito; Asao Katsume; Ken-ichi Akamatsu; Yoshiyuki Ohsugi; Hitoshi Shiozaki; Morito Monden
- Book ID
- 102654673
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 862 KB
- Volume
- 68
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Interleukin-6 (IL-6) has been reported to be responsible for the loss of lean body mass during cancer cachexia in colon-26 adenocarcinoma (C-26)-bearing mice. This study was carried out to elucidate the intracellular proteolytic pathways operating in skeletal muscle in C-26bearing mice, and to examine the effect of anti IL-6 receptor antibody on muscle atrophy. On day I 7 after tumor inoculation, trocnemius muscle weight of C-26-bearing mice had the sign' I F = icantly decreased to 69% of that of the pair-fed control mice. This weight loss occurred in association with increases in the mRNA levels of cathepsins B and L, poly-ubiquitin (Ub) and the subunits of proteasomes in the muscles. Furthermore, enzymatic activiky of cathepsin B+L in the muscles also increased to 119% of the control. The administration of antimurine IL-6 receptor antibody to C-26-bearing mice reduced the weight loss of the gastrocnemius muscles to 84% of that of the control mice, whose enzymatic activity of cathepsin B+L and mRNA levels of cathepsin L and poly-Ub were significantly suppressed compared with those of the C-26-bearing mice. Our data indicate that both the lysosomal cathepsin pathway and the ATP-dependent proteolytic pathway might be invoked in the muscle atrophy of C-26-bearing mice. The results also suggest that anti IL-6 receptor antibody could be a potential therapeutic agent against muscle atrophy in cancer cachexia by inhibiting these proteolytic systems.