Study On The Relationship Between Protein Degradation And NF - κB / MuRF1 In Skeletal Muscle Caused By Hypoxia Training In Different Models

Objective:The effect and interaction on decomposition metabolism of rats’skeletal muscles under hypoxic exposure, intensive training and simulated altitude training were discussed. The biological mechanism of adjustment on skeletal muscle protein decomposition was investigated. The difference on skeletal muscle protein metabolism between simulated altitude training and simulated living high-training low processes was compared, in order to provide experimental evidence for further study of interference of skeletal muscle protein decomposition in hypoxic exercising processes.Experimental SectionAfter 3 days adapting culture under quite environment, rats were randomly chosen to normoxic control group (C, n=10), normoxic exercising group (E, n=20), hypoxic control group (HC. n=20), hypoxic exercising group (HE. n=20). and hypoxic interval exercising group (HiLo, n=20). The rats were treated with 13.6% hypoxic exposure and/or 90% LT weight swimming exercise. The amount of Pro, Myo, TNF-α, NF-κB, IkBα and the expression of MAFbx, MuRF1, IKKβ mRNA in skeletal muscles after two and six weeks were measured.Result and Discussion(1) Through double factor variance analysis among C, E, HC and HE, we found that two weeks’hypoxic exposure obviously decreases Pro and Myo in skeletal muscle (P<0.05) significantly increases the relative expression of MAFbx mRNA (P<0.01) and the amount of NF-κB (P<0.01). and obviously increases TNF-α (P<0.05). Although hypoxic exposure can increase the relative expression of MuRF1 mRNA and IKKP mRNA, and decrease IkBa in skeletal muscle, no significant differences were observed (P>0.05). Two weeks’exercise can decrease Pro. Myo. TNF-α and IkBa in skeletal muscles, but the changes were not significant (P>0.05). Hypoxic exercise has significant effect on further decreasing Pro (P<0.05) and increasing the relative expression of IKKβ mRNA (P<0.01) in skeletal muscles. However, hypoxic exposure has no significant effect on decreasing Myo. IkBα. or increasing TNF-α, NF-κB and relative expression of IKKβ mRNA and MuRF1 mRNA (P>0.05)(2) After two weeks’ experiment, comparing to HE group, HiLo group has an increased Pro (P<0.05) and Myo (P>0.05), a decreased relative expression of MAFbx mRNA and MuRF1 mRNA (P<0.01), and a decreased amount of TNF-α and NF-κB (P<0.05) in skeletal muscles. The relative expression of IKKβ mRNA decreased while IkBa increased, but the changes were not significant (P>0.05)(3) Through double factor variance analysis among C. E, HC and HE, we found that six weeks’ hypoxic exposure obviously decreases Pro and Myo in skeletal muscle (P<0.05) significantly increases the relative expression of MAFbx mRNA (P<0.01), MuRF1 mRNA (P<0.01), IKKβ mRNA (P<0.01) and the amount of TNF- (P<0.01) and NF-κB (P<0.01), and decreases IkBa (P<0.05) in rat skeletal muscles. Six weeks’exercise can significantly decrease Pro (P<0.01) and Myo (P<0.05), significantly increase the relative expression of MAFbx mRNA (P<0.05) and IKKβ mRNA (P<0.01) in skeletal muscles. The increase of TNF-α and NF-κB and decrease of IkBa is not significant (P>0.05). Hypoxic exercise has no significant effect on further decreasing Pro and Myo, or increasing TNF-a, NF-κB and relative expression of MuRF1 mRNA (P>0.05) in skeletal muscles. It has significant effect on further increasing the relative expression of MAFbx mRNA (P<0.05)、IKKβ mRNA (P<0.01) and decreasing IkBa (P<0.01) in skeletal muscles.(4) After two weeks’experiment, comparing to HE group, HiLo group has a significantly increased Pro (P<0.05) and Myo (P<0.05), a decreased relative expression of MAFbx mRNA, MuRF1 mRNA (P<0.01) and IKKp mRNA (P<0.05), and a decreased amount of TNF-a and NF-κB (P<0.05) in skeletal muscles. The amount of IkBa increased, but the change was not significant (P>0.05)Conclusion(1) Simulated altitude training will decrease skeletal muscle proteins, training and exposure time.and degree of reduction increased with the increase time of training and/or hypoxic exposure.(2) Simulated altitude training can enable TNF-α/NF-κB/MuRF1 pathway, and enhance the decomposition metabolism of skeletal muscle proteins. This may be a mechanism that altitude training decreases skeletal muscle proteins.(3) Living high-training low can reduce the enabling of TNF-α/NF-KB/MuRF1 pathway, and thus reduce the decomposition metabolism of skeletal muscle proteins, which is important in preventing skeletal muscle protein loss caused by altitude training.