Anchoring skeletal muscle development and disease: the role of ankyrin repeat domain containing proteins in muscle physiology

The ankyrin repeat is a protein module with high affinity for other ankyrin repeats based on strong Van der Waals forces. The resulting dimerization is unusually resistant to both mechanical forces and alkanization, making this module exceedingly useful for meeting the extraordinary demands of muscle physiology. Many aspects of muscle function are controlled by the superfamily ankyrin repeat domain containing proteins, including structural fixation of the contractile apparatus to the muscle membrane by ankyrins, the archetypical member of the family. Additionally, other ankyrin repeat domain containing proteins critically control the various differentiation steps during muscle development, with Notch and developmental stage-specific expression of the members of the Ankyrin repeat and SOCS box (ASB) containing family of proteins controlling compartment size and guiding the various steps of muscle specification. Also, adaptive responses in fully formed muscle require ankyrin repeat containing proteins, with Myotrophin/V-1 ankyrin repeat containing proteins controlling the induction of hypertrophic responses following excessive mechanical load, and muscle ankyrin repeat proteins (MARPs) acting as protective mechanisms of last resort following extreme demands on muscle tissue. Knowledge on mechanisms governing the ordered expression of the various members of superfamily of ankyrin repeat domain containing proteins may prove exceedingly useful for developing novel rational therapy for cardiac disease and muscle dystrophies

The impact of diabetes on the pathogenesis of sepsis

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones

Adaptations in antagonist co-activation: Role in the repeated-bout effect

Eccentric exercise results in an adaptation which attenuates muscle damage from subsequent exercise—termed the “repeated-bout effect (RBE).” Purpose: Study examined antagonist co-activation and motor-unit recruitment strategy, assessed via dEMG, concomitant to the RBE. Methods: Nine participants performed 5 sub-maximal isometric trapezoid (ramp-up, hold, ramp-down) contractions at force levels corresponding to 50% and 80% of maximal isometric strength (MVC). Surface EMG signals of the biceps brachii were decomposed into individual motor-unit action potential trains. The relationship between mean firing rate (MFR) of each motor-unit and its recruitment threshold (RT) was examined using linear regression. Eccentric exercise was then performed until biceps brachii MVC had decreased by ~40%. Surface EMG of the biceps and triceps were collected during eccentric exercise. MVC, range-of-motion (ROM), and delayed onset muscle soreness (DOMS) were measured 24-hours, 72-hours, and 1-week following eccentric exercise. Three weeks later all procedures were repeated. Results: Changes in MVC (-32±14% vs -25±10%; p = 0.034), ROM (-11% vs 6%; p = 0.01), and DOMS (31.0±19mm vs 19±12mm; p = 0.015) were attenuated following the second bout of exercise. Triceps EMG was reduced (16.8±9.5% vs. 12.6±7.2%; p = 0.03) during the second bout of eccentric exercise. The slope (-0.60±0.13 vs -0.70±0.18; p = 0.029) and y-intercept (46.5±8.3 vs 53.3±8.8; p = 0.020) of the MFR vs. RT relationship was altered during contractions at 80% of MVC prior to the second bout of eccentric exercise. No changes were observed at 50% of MVC. Conclusion: A reduction in antagonist co-activation during the second bout of eccentric exercise suggests less total force was required to move an identical external load. This finding is supported by the increased negative slope coefficient and an increased y-intercept of the linear relationship between RT and MFR.Funded by University of Oklahoma Graduate College Robberson Grant.Ye