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Beta-lapachone attenuates immobilization-induced skeletal muscle atrophy in mice.

Abstract：

: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 H2O2 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.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Park S,Shin MG,Kim JR,Park SY

doi

10.1016/j.exger.2019.110711

subject

Has Abstract

pub_date

2019-10-15 00:00:00

pages

110711

eissn

0531-5565

issn

1873-6815

pii

S0531-5565(19)30175-5

journal_volume

126

pub_type

杂志文章

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Beta-lapachone attenuates immobilization-induced skeletal muscle atrophy in mice.