Mitochondria are dynamic organelles forming a tubular network that is continuously fusing and dividing to control their morphology and functions. Recent literature has shed new light on a potential link between the dynamic behavior of mitochondria and muscle development. In this study, we investigate the role of mitochondrial fission factor dynamin-related protein 1 (Drp1) in myogenic differentiation. We found that differentiation of C2C12 myoblasts induced by serum starvation was accompanied by a gradual increase in Drp1 protein expression (to ∼350% up to 3 days) and a fast reduction of Drp1 phosphorylation at Ser-637 (to ∼30%) resulting in translocation of Drp1 protein from the cytosol to mitochondria. During differentiation, treatment of myoblasts with mitochondrial division inhibitor ( mdivi-1), a specific inhibitor of Drp1 GTPase activity, caused extensive formation of elongated mitochondria, which coincided with increased apoptosis evidenced by both enhanced caspase-3 activity and increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Furthermore, the mdivi-1-treated myotubes ( day 3 in differentiation media) showed a reduction in mitochondrial DNA content, mitochondrial mass, and membrane potential in a dose-dependent manner indicating defects in mitochondrial biogenesis during myogenic differentiation. Most interestingly, mdivi-1 treatment significantly suppressed myotube formation in both C2C12 cells and primary myoblasts. Likewise, stable overexpression of a dominant negative mutant Drp1 (K38A) dramatically reduced myogenic differentiation. These data suggest that Drp-1-dependent mitochondrial division is a necessary step for successful myogenic differentiation, and perturbation of mitochondrial dynamics hinders normal mitochondrial adaptations during muscle development. Therefore, in the present study, we report a novel physiological role of mitochondrial dynamics in myogenic differentiation.
Reported secondary conditions of physical deconditioning and isolation are inversely related to the ability of moderately impaired women with physical disabilities to participate in LTPA when functional status was controlled and should be considered in efforts to increase involvement in this health promoting behaviour.
Sedentary, eumenorrheic women (N = 27) 22 to 40 years of age, with high baseline levels of plasma high-density lipoprotein cholesterol, were randomly assigned to a walking (n = 16) or a control group (n = 11). The training program involved treadmill walking 4.8 km (3.0 miles) four times a week for 40 weeks at a mean intensity of 72% maximal heart rate. Aerobic power (VO2max) was improved by 22%, but no training effect was observed in body composition variables or blood lipid/lipoprotein levels. Despite additional increments in exercise intensity over the final 20 weeks of training, most of the improvement in VO2max was observed over the first 20 weeks of the study. Exercising subjects' baseline levels of plasma HDL-C were found to be inversely associated with the change (delta) scores in the lipoprotein (r = -0.51, p < or = .05).
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