Denervation atrophy

Furuno, K., Goodman, M. N., and Goldberg, A, L. (1990). Role of different proteolytic systems in the degradation of muscle proteins during denervation atrophy. /. Biot. Chem,... 

Increased concentrations of muscle cathepsins have been recorded in many types of muscle atrophy. Acid cathepsin activity increases in dystrophic mouse muscle (W12) and in muscle from Duchenne-type dystrophy (P6) in the latter investigation, the elevation tended to be greater in the more advanced cases. Elevated acid cathepsin has been recorded also in denervation atrophy and vitamin E deficiency. Alkaline cathepsin activity has been shown to be higher in the dystrophic mouse (P7) and in Duchenne dystrophy (P12). 

G12. Graff, G. L. A., Hudson, A. J., and Strickland, K. P., Biochemical changes in denervated skeletal muscle. I. Effect of denervation atrophy on the main phosphate fractions of the rat gastrocnemius muscle. Biochim. Biophys. Acta 104, 524-531 (1965). 

Muscle fibers also atrophy following neonatal denervation. Treatment with ACTH 4-10 but not with a-MSH, exacerbates the muscle atrophy in 7 day old neonates. By 15 days, however, both melanocortins effect an increase in muscle fiber diameter, overcoming the denervation atrophy seen in the saline-treated controls. A comparison of muscle fiber diameters from 15 day old lesioned neonates treated with melanocortins shows them to be comparable in size to normal saline-treated pups of the same age (Table 7). 

Goldspink DF, Garlick PJ, McNurlan MA (1983) Protein turnover measured in vivo and in vitro in muscles undergoing compensatory growth and subsequent denervation atrophy. Biochem J... 

Indefinable are the terms "normal aged person" or "normal-control aged person." In muscle biopsies of aging persons we nearly always have observed different combinations and various degrees of denervation atrophy and/or type-2 fiber atrophy (see below). 

There are two major categories of muscle-fiber atrophy (a) ordinary denervation atrophy... 

In HIV there is often a complex pathogenesis of the muscle atrophy, which histochemically is type-2 fiber atrophy with or without denervation atrophy. It can have five components (a) neuropathic, viz. dysimmune dysschwannian denervation neuropathy early in the course of the disease, and virogenic toxicity causing dysneuronal neuropathy later (b) often cachexia (c) hypomotUity/disuse (d) possible nerve toxicity of anti-HIV dmgs (e) infrequently, myotoxicity from viral products. With HIV, type-2 fiber atrophy in response to a hyponutri-tional/cachectic aspect would be altmistic, but when in response to the other causes it would not be. 

Sacheck JM, Hyatt JP, Raffaello A et al. (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. PASEB J 21, 140-155. 

Although not directly relevant to sarcopenia, a similar protective effect from denervation atrophy was observed in transgenic mice overexpressing PGC-la in this case, PGC-la reduced the activation of F0X03 and the expression of the atrophy-related ubiquitin ligases atrogin-1 and MURF-1 [60]. 

While cared for in the ICU, critically ill patients can develop muscle weakness and, occasionally, paralysis. Some of these patients have evidence of axonal degeneration (Table 2) and denervation atrophy (Fig. 10) (40). This constellation of findings is known as critical illness polyneuropathy. Sepsis and multiple organ failure, although common in these patients, are not essential prerequisites for the development of critical illness polyneuropathy (40). In other patients, rather than axonopathy, there is evidence of isolated myopathy (critical illness myopathy) (Fig. 11) (40). Patients developing isolated myopathy have often been treated with steroids and neuromuscular blocking agents (40). 

Medina, R., Wing, S.S., and Goldberg, A.L., Increase in levels of polyubiquitin and proteasome niRNA in skeletal muscle during starvation and denervation atrophy, Biochem J, 307 (Pt 3), 631, 1995. 

In denervation atrophy, on the other hand, a much simpler change is seen, consisting merely of a progressive reduction in size of the muscle fibres. In diseases where the motor units are affected one at a time, the remaining healthy fibres may markedly increase in size, probably as a result of work... 

Both muscular dystrophy (human and animal) and denervation atrophy are associated with increased concentrations of proteolytic enzymes in muscle. The likelihood that this is related to the enhanced protein turnover is clear, but evidence is scanty. Both acid [65, 82, 83] and alkaline [66, 83, 84] cathepsin activity increase in dystrophic muscle and either or both may be important in this respect. 

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