Fig. 3

Skeletal muscle morphological alterations in cancer cachexia revealed by confocal (a–d) and transmitted electron (e, f) microscopic examination of a cross section of soleus muscle from mouse bearing B16 melanoma and severe cachexia as compared to normal soleus obtained from control C57BL/6 mouse. Myocyte apoptotic cell death is characterized by DNA fragmentation and deposition of chromatin masses around nuclear membrane. In a, a representative image illustrating the normal flattened nuclei located in parallel with skeletal muscle fibers in the periphery of normal myotube. In b, the image shows irregular nucleus with visible clumping of nuclear chromatin confirming cell death by apoptosis. In c, the micrograph shows the myosin banding displaying regular cross-striations and intense fluorescence. In d, illustrates myosin appearance in cachectic skeletal muscle fiber. The weak fluorescence intensity is reflecting breakdown of myofibril and tissue architecture. Nuclei were stained with propidium iodide and myosin pattern was revealed with monoclonal antibody to fast myosin skeletal heavy chain (lower panel). In e, the electron micrograph shows a nucleus with normal morphology (upper side) and a typical apoptotic nucleus with condensed chromatin fragments at its periphery (lower side). In f, the micrograph shows a portion of sarcolemma surrounded by mitochondria and vacuoles containing apoptotic bodies (autophagosome). The ubiquitin–proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle degradation along skeletal muscle wasting