@entity2383 during progression of XXXX .

@entity296 @entity19 @entity3986 @entity1372 @entity1555 @entity205 @entity299 @entity141 @entity121 @entity2383
UNASSIGNED: @entity1555 ( @entity1555 ) is a progressive @entity121 with severe @entity299 . It is believed that cellular oxidative stress and augmented @entity141 signaling drives the development of cardiac pathology. Some @entity2383 have also been reported. Here we investigate cellular mechanisms responsible for impaired mitochondrial metabolism in @entity296 at early stages of the disease. We employed electrophysiological and imaging techniques to study mitochondrial structure and function in cardiomyocytes from mdx @entity19 , an animal model of @entity1555 . Here we show that mitochondrial matrix was progressively oxidized in myocytes isolated from mdx @entity19 . Moreover, an abrupt increase in workload resulted in significantly more pronounced oxidation of mitochondria in dystrophic cells. Electron micrographs revealed a gradually increased number of damaged mitochondria in mdx myocytes. Degradation in mitochondrial structure was correlated with progressive increase in mitochondrial @entity141 sequestration and mitochondrial depolarization, despite a substantial and persistent elevation in resting cytosolic @entity1372 levels. Treatment of mdx cells with @entity205 , an inhibitor of mitochondrial permeability transition pore (mPTP), shifted both resting and workload-dependent mitochondrial redox state to the levels recorded in control myocytes. It also significantly reduced workload dependent depolarization of mitochondrial membrane in @entity3986 . Overall, our studies highlight age dependent deterioration of mitochondrial function in @entity3986 , which seems to be associated with excessive opening of mPTP due to oxidative stress and cellular @entity141 overload.
