Effects Of Hypoxic Exercise On MTOR/p70S6K Signaling Pathway In Rat Skeletal Muscle

Objective: The present thesis designed an animal exercise protocol of hypoxic endurance, to study the regulation of mammalian target of rapamycin (mTOR) pathway in 4 weeks hypoxic exercise, and the relation between mTOR pathway and skeletal muscular protein synthesis.Methods: Adult male Sprague-Dawley rats (12 weeks old) were randomly divided into four groups: normoxia sedentary group (NS), normoxia Exercise group (NE), hypoxic sedentary group (HS), hypoxic exercise group (HE). The hypoxia circumstance was normal pressure hypoxia, oxygen concentration is 13.6%, it equivalently 3500m above sea level. HS and HE group constantly lived in hypoxia. NS group was remained 28 days sedentary at normoxia. HE, HS and HE group all divided into four groups as 3 day, 7 day, 14 day and 28 day group. The exercise group performed 3 days, 7 days, 14 days or 28 days endurance exercise, HS group all remained sedentary at hypoxia. Total protein content, mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) total protein, p70S6K (Thr389) phosphorylation of extensor digitorum longus (EDL) muscle were determined by Bradford and Western blot.Results: (1) After 28 days, both the body weight of HE and NE group less than NS group (82.9%, P<0. 01; 87.7%, P<0. 01, respectively), HS group less than NS group (92. 1%, P<0. 01). (2) After 3 days, there was no difference between all groups about the total protein content. After 7 days, total protein content of NE group was higher than HS (109. 7%, P<0.01) and HE group (111.6%, P<0.01). And after 14 days, HE (121.1%, P<0.01) and NE (117.4%, P<0.01) group was higher than HS group. (3) Hypoxia significantly inhibition mTOR (P<0. 01) and p70S6K total protein (P<0. 05) after 3rd day. Exercise promote mTOR total protein significantly (P<0. 01), but hypoxia inhibition it significantly (P<0. 01). After 14 days, hypoxia inhibition mTOR total protein significantly (P<0. 01) and p70S6K (Thr389) phosphorylation (P<0. 01), but exercise promote p70S6K total protein very significantly (P<0. 01). After 28 days, hypoxia inhibition mTOR total protein significantly (P<0.05) and p70S6K (Thr389) phosphorylation (P<0.01), but exercise significantly promote mTOR (P<0. 01) and p70S6K total protein (P<0. 05).Conclusions: (1) Hypoxia inhibited muscular protein synthesis, while normoxic exercise promoted muscular protein synthesis. (2) Four weeks hypoxia inhibited mT0R/p70S6K pathway, but exercise could elevated it. Hypoxic exercise could reduce the inhibiting effective of hypoxia on mTOR/p70S6K pathway. (3) Hypoxic exercise had of time course effective on mTOR and p70S6K. In the initial stage of hypoxia, the mTOR/p70S6K pathway of muscle had been inhibited; in the midanaphase of hypoxia, intensive effective of hypoxic exercise on the mT0R/p70S6K pathway was gradually manifest. (4) In four weeks exercise, the time course effective was difference between total protein of mTOR and p70S6K.