title: A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.
abstract: It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12m/min, 2h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice.
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Furuya
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Juan Alejandro
authors.initials: JA
authors.lastname: Oliva Trejo
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Takeda-Ezaki
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Mineki
authors.affiliation: Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Taka
authors.affiliation: Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan; Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan; Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan; Translational Research Center, Fukushima Medical University, Fukushima 960-1295, Japan. Electronic address: jezaki@fmu.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Ezaki
mesh_terms: D000818:Animals; D001343:Autophagy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012420:Running; D015398:Signal Transduction; D013217:Starvation; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C546843:mTOR protein, mouse; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: Autophagy; Exercise; GFP-LC3; Skeletal muscle; Treadmill; mTor