Molecular mechanism underlying muscle mass retention in hibernating bats: role of periodic arousal.
Hibernators like bats show only marginal muscle atrophy during prolonged hibernation. The current study was designed to test the hypothesis that hibernators use periodic arousal to increase protein anabolism that compensates for the continuous muscle proteolysis during disuse. To test this hypothesis, we investigated the effects of 3-month hibernation (HB) and 7-day post-arousal torpor (TP) followed by re-arousal (RA) on signaling activities in the pectoral muscles of summer-active (SA) and dormant Murina leucogaster bats. The bats did not lose muscle mass relative to body mass during the HB or TP-to-RA period. For the first 30-min following arousal, the peak amplitude and frequency of electromyographic spikes increased 3.1- and 1.4-fold, respectively, indicating massive myofiber recruitment and elevated motor signaling during shivering. Immunoblot analyses of whole-tissue lysates revealed several principal outcomes: (1) for the 3-month HB, the phosphorylation levels of Akt1 (p-Akt1) and p-mTOR decreased significantly compared to SA bats, but p-FoxO1 levels remained unaltered; (2) for the TP-to-RA period, p-Akt1 and p-FoxO1 varied little, while p-mTOR showed biphasic oscillation; (3) proteolytic signals (i.e., atrogin-1, MuRF1, Skp2 and calpain-1) remained constant during the HB and TP-to-RA period. These results suggest that the resistive properties of torpid bat muscle against atrophy might be attained primarily by relatively constant proteolysis in combination with oscillatory anabolic activity (e.g., p-mTOR) corresponding to the frequency of arousals occurring throughout hibernation.
Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju, Gangwon-Do, Republic of Korea.
Kisoo
K
Lee
Hyekyoung
H
So
Taesik
T
Gwag
Hyunwoo
H
Ju
Ju-Woon
JW
Lee
Masamichi
M
Yamashita
Inho
I
Choi
D000818:Animals; D001143:Arousal; D015153:Blotting, Western; D001831:Body Temperature; D002154:Calpain / Q000378:metabolism; D002685:Chiroptera / Q000378:metabolism*; D004576:Electromyography; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006605:Hibernation; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D010369:Pectoralis Muscles / Q000378:metabolism* / Q000473:pathology; D010507:Periodicity; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012621:Seasons; D012768:Shivering; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D051858:Forkhead Transcription Factors; D020672:I-kappa B Proteins; D009124:Muscle Proteins; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D002154:Calpain