Abstract
We hypothesized that curcumin may mitigate muscle protein degradation and loss through attenuation of proteolytic activity in limb muscles of mice exposed to reloading (7dR) following immobilization (7dI). In gastrocnemius of mice (female C57BL/6J, 10 weeks) exposed to recovery following a seven-day period of hindlimb immobilization with/without curcumin treatment, markers of muscle proteolysis (systemic troponin-I), atrophy signaling pathways and histone deacetylases, protein synthesis, and muscle phenotypic characteristics and function were analyzed. In gastrocnemius of reloading mice compared to unloaded, muscle function, structure, sirtuin-1, and protein synthesis improved, while proteolytic and signaling markers (FoxO1/3) declined. In gastrocnemius of unloaded and reloaded mice treated with curcumin, proteolytic and signaling markers (NF-kB p50) decreased and sirtuin-1 activity and hybrid fibers size increased (reloaded muscle), while no significant improvement was seen in muscle function. Treatment with curcumin elicited a rise in sirtuin-1 activity, while attenuating proteolysis in gastrocnemius of mice during reloading following a period of unloading. Curcumin attenuated muscle proteolysis probably via activation of histone deacetylase sirtuin-1, which also led to decreased levels of atrophy signaling pathways. These findings offer an avenue of research in the design of therapeutic strategies in clinical settings of patients exposed to periods of disuse muscle atrophy.
Highlights
In chronic disease and cancer, disuse muscle atrophy is common in the affected patients as a result of physical inactivity [1,2,3,4,5]
Disuse muscle atrophy is relevant in patients with chronic conditions and during prolonged Disuse atrophy is relevant in patients with trauma, chronic conditions during prolonged bed bed rest duemuscle to surgical interventions, critical illness, and acute and exacerbations of chronic rest due to surgical interventions, critical illness, trauma, and acute exacerbations of chronic conditions
A significant increase in protein synthesis as measured by puromycin-labeled proteins was observed in the limb muscles of the immobilized control mice treated with curcumin. These findings suggest that curcumin somehow contributes to preventing proteolysis, while favoring protein synthesis in the control muscles in the current experimental model
Summary
In chronic disease and cancer, disuse muscle atrophy is common in the affected patients as a result of physical inactivity [1,2,3,4,5]. Patients with chronic diseases are exposed to periods of prolonged bed rest due to acute exacerbations, which further contribute to worsen muscle atrophy in those individuals. Muscle atrophy is common during critical illness that further impairs muscle mass in the patients. Bone fractures and surgical interventions are frequent, which altogether deteriorates muscle mass and performance in the patients. Disuse muscle atrophy imposes a tremendous burden on the health-care systems as the recovery of muscle mass and function can only be attained following strict long-term rehabilitation programs.
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