Several lines of evidence suggest that
free radical mediated injury and oxidative stress may lead to muscle
necrosis in the
muscular dystrophies, including those related to defects in the
dystrophin gene. We have examined muscle cell death using an in vitro assay in which the processes that lead to myofiber
necrosis in vivo may be amenable to investigation in a simplified cell culture system. Using myotube cultures from normal and
dystrophin-deficient (mdx) mice, we have examined the susceptibilities of the cells to different metabolic stresses.
Dystrophin-deficient cells were more susceptible to
free radical induced injury when compared to normal cells, but the two populations were equally susceptible to other forms of metabolic stress. The differential response appeared to be specifically related to
dystrophin expression since undifferentiated myoblasts (which do not express
dystrophin) from normal and mdx mice were equally sensitive to oxidative stress. Thus, the absence of
dystrophin appears to render muscle specifically more susceptible to
free radical induced injury. These results support the hypothesis that oxidative stress may lead to myofiber
necrosis in these disorders. Elucidating the mechanisms leading to cell death may help to explain the variabilities in disease expression that are seen as a function of age, among different muscles, and across species in animals with
muscular dystrophy due to
dystrophin deficiency.