Role of contraction-induced injury in the mechanisms of muscle damage in muscular dystrophy.
1. Duchenne muscular dystrophy (DMD) is a severe disease of skeletal muscle, characterized by an X-linked recessive inheritance and a lack of dystrophin in muscle fibres. It is associated with progressive and severe wasting and weakness of nearly all muscles and premature death by cardiorespiratory failure. 2. Studies investigating the susceptibility of dystrophic skeletal muscles to contraction-mediated damage, especially after lengthening actions where activated muscles are stretched forcibly, have concluded that dystrophin may confer protection to muscle fibres by providing a mechanical link between the contractile apparatus and the plasma membrane. In the absence of dystrophin, there is disruption to normal force transmission and greater stress placed upon myofibrillar and membrane proteins, leading to muscle damage. 3. Contraction protocols (involving activation and stretch of isolated muscles or muscle fibres) have been developed to assess the relative susceptibility of dystrophic (and otherwise healthy) muscles to contraction-induced injury. These protocols have been used successfully to determine the relative efficacy of different (gene, cell or pharmacological) interventions designed to ameliorate or cure the dystrophic pathology. More research is needed to develop specific 'contraction assays' that will assist in the evaluation of the clinical significance of different therapeutic strategies for muscular dystrophy.
Lynch
Gordon S
GS
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia. gsl@unimelb.edu.au
D000818:Animals; D016189:Dystrophin / Q000172:deficiency; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000503:physiopathology*
D016189:Dystrophin