Exp Gerontol 2019 10 24;126:110711. Epub 2019 Aug 24.
Department of Physiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, Daegu, Republic of Korea. Electronic address:
Skeletal muscle atrophy reduces quality of life and increases morbidity and mortality in patients with chronic conditions. Oxidative stress is a key factor contributing to skeletal muscle atrophy by altering both protein synthesis and protein degradation pathways. Beta-lapachone (Beta-L) is known to act as a pro-oxidant in cancer cells but suppresses oxidative stress in normal cells and tissues. In the present study, we examined whether Beta-L (100 mg/kg body weight) prevents immobilization-induced skeletal muscle atrophy in male C57BL/6N mice. Skeletal muscle atrophy was induced by immobilization of left hindlimbs for two weeks, and right hindlimbs were used as controls. The muscle weights of gastrocnemius (0.132 ± 0.003 g vs. 0.115 ± 0.003 g in Beta-L and SLS, respectively, p < 0.01) and tibialis anterior (0.043 ± 0.001 vs. 0.027 ± 0.002 in Beta-L and SLS, respectively, p < 0.001) were significantly heavier in Beta-L-treated mice than that in SLS-treated mice in immobilization group, which was accompanied by improved skeletal muscle function as tested by treadmill exhaustion and grip strength test. Immobilization increased HO levels, while Beta-L treatment normalized such levels (1.6 ± 0.16 μM vs. 2.7 ± 0.44 μM in Beta-L and vehicle, respectively, p < 0.05). Oxidative stress makers were also normalized by Beta-L treatment. Protein synthesis signaling pathways were unaltered in the case of both immobilization and Beta-L treatment. However, protein catabolic, ubiquitin-proteasomal, and autophagy-lysosomal pathways were stimulated by immobilization and were normalized by Beta-L treatment. Upregulation of transforming growth factor β and Smad 2/3 after immobilization was significantly diminished by Beta-L treatment. These results suggest that Beta-L attenuates the loss of muscle weight and function induced by immobilization through suppression of oxidative stress.