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EBioMedicine. 2018 Nov;37:499-508. doi: 10.1016/j.ebiom.2018.10.057. Epub 2018 Nov 1.

Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle Atrophy.

Author information

1
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,; Organization for University Research Initiatives, Waseda University, Tokyo, Japan.
2
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
3
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,. Electronic address: shibatas@waseda.jp.

Abstract

BACKGROUND:

Atrogin1, which is one of the key genes for the promotion of muscle atrophy, exhibits day-night variation. However, its mechanism and the role of its day-night variation are largely unknown in a muscle atrophic context.

METHODS:

The mice were induced a muscle atrophy by hindlimb-unloading (HU). To examine a role of circadian clock, Wild-type (WT) and Clock mutant mice were used. To test the effects of a neuronal effects, an unilateral ablation of sciatic nerve was performed in HU mice. To test a timing-dependent effects of weight-bearing, mice were released from HU for 4 h in a day at early or late active phase (W-EAP and W-LAP groups, respectively).

FINDINGS:

We found that the day-night oscillation of Atrogin1 expression was not observed in Clock mutant mice or in the sciatic denervated muscle. In addition, the therapeutic effects of weight-bearing were dependent on its timing with a better effect in the early active phase.

INTERPRETATION:

These findings suggest that the circadian clock controls the day-night oscillation of Atrogin1 expression and the therapeutic effects of weight-bearing are dependent on its timing. FUND: Council for Science, Technology, and Innovation, SIP, "Technologies for creating next-generation agriculture, forestry, and fisheries".

KEYWORDS:

Atrogin1; Chrono-exercise; Circadian rhythm; Hindlimb-unloading; Weight-bearing

PMID:
30391495
PMCID:
PMC6286653
DOI:
10.1016/j.ebiom.2018.10.057
[Indexed for MEDLINE]
Free PMC Article

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