Ca² - Activated Proteinases, Protein Degradation and Muscular Dystrophy

Abstract

Progressive muscular dystrophies in man are characterised by muscle degeneration and weakness. A gradual loss of muscle tissue takes place until, in the late stages of most dystrophies (and particularly in the X-linked Duchenne type), very little functional muscle remains. During necrosis, there is a marked loss of both myofibrillar and soluble proteins from the muscle fibres. While the underlying causes may in part be related to membrane defects (1), alterations in protein turnover in the muscle tissue must be involved in the development of the condition to some extent. The level of protein in any tissue is determined, under steady state conditions, as a balance between the rate of protein synthesis and its rate of degradation. The observed loss of muscle mass in wasting disorders would appear then to be explained most readily by an increase in the rate of protein degradation and, indeed, such measurements have been made in patients with Duchenne dystrophy (2). However, the same net effect i.e. muscle degeneration, can be achieved as a result of a diminished rate of protein synthesis in muscle and very recently, measurements made in vivo with dystrophic boys have suggested that in all types of dystrophy, muscle protein synthesis is depressed and that there is little change in protein breakdown from the rates observed with unafflicted male patients (3).