The changes of HIF-1α and AMPKα2 expression levels during skeletal muscle blunt injury recovery

doi:10.13459/j.cnki.cjap.2016.03.018

Abstract

Abstract: Objective:To explore the possible biological mechanisms of skeletal muscle injury recovery by observing the changes of AMP-activated protein kinase α2 (AMPKα2) and hypoxia inducible factor-1α (HIF-1α) expression levels of rats in the skeletal muscle blunt injury recovery process. Method:Six of the 48 male Wistar rats was randomly selected as the normal control group. The blunt injury model was set up by injuring the hind legs of remaining 42 rats with heavy objects. Then they were divided into 7 groups (n=6). The changes of AMPKα2 and HIF-1α expression levels were tested in the hind limb triceps surae of the model rats from each of the 7 groups at 12 hours, 2 days, 5 days, 7 days, 10 days, 15 days and 30 days respectively following the injury. Results:The expression levels of AMPKα2 and HIF-1α all increased significantly at 12 hours following the injury and fell close to normal levels at 15 days following the injury. The values of AMPKα2 and HIF-1α expression peaked within 2 days after injury and the expression levels began to decline at 5 days after injury. Except the peak, the changes of the mRNA expressions of the two proteins were basically consistent with those of protein expression at the other time points. Conclusion:HIF-1α and AMPKα2 might play roles in mediating hypoxia adaptation, muscle cell regeneration, and energy compensation to promote recovery after injury.

Key words: skeletal muscle blunt injury, AMPKα2, HIF-1a, mitochondrial autophagy, the energy compensation, mouse

WEN Han, GE Xin-fa, DONG Gui-jun, PANG Hong-bo, ZHANG Li-hui. The changes of HIF-1α and AMPKα2 expression levels during skeletal muscle blunt injury recovery[J]. CJAP, 2016, 32(3): 260-263.

References

[1] 亓建洪. 运动创伤学[M]. 北京:人民军医出版社, 2008:1-2.
[2] Beiner JM, Jokl P. Muscle injuries:current treatment option[M]. Am Acad Orthop Surg, 2001, 9(4):227-237.
[3] Leeder J, Spence J, Taylor E, et al. The effect of electrical stimulation on recovery from exercise-induced muscle damage[J]. Br J Sports Med, 2011, 45(15):A21.
[4] 董贵俊, 葛新发, 李可峰, 等. 磁场定位磁纳米化bFGF治疗大鼠腓肠肌钝挫伤恢复效果研究[J]. 武汉体育学院学报, 2011, 45(2):43-46.
[5] Kenneth G, Rice Jacgueline P, Dellwo. Within-semester sta-bility and adjustment correlates of the multidimensional per-fe ctionism scale[J]. Meas Evalu in Coma Dev, 2001, 34(3):146-156.
[6] 汤强, 姜文凯, 盛蕾, 等. 低氧高强度训练下大鼠骨骼肌糖酵解酶活性和HIF-1α表达的变化[J]. 体育与科学, 2009, 30(2):62-67.
[7] Hardie, DG, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily:Metabolic sensors of the eu-karyotic cell[J]. Annu Rev Biochem, 1998, 67:821-855.
[8] Kudo N, Barr AJ, Barr RL, et al. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5'-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase[J]. J Biol Chem, 1995, 270(29):17513-17520.
[9] Hardie DG, Scott JW, Pan DA, et al. Management of cellu-lar energy by the AMP-activated protein kinase system[J]. FEBS Lett, 2003, 54(6):113-120.
[10] Zhang BB, Zhou G, Li C. AMPK:an emerging drug target fo r diabetes and the metabolic syndrome[J]. Cell Metab, 2009, 9(5):407-416.
[11] Kubis HP, Hanke N, Scheibe RJ, et al. Accumulation and nuclear import of HIF1 alpha during high and low oxygen concentration in skeletal muscle cells in primary culture[J]. Biochim Biophys Acta, 2005(2), 1745:187-195.
[12] Stroka DM, Burkhardt T, Desbaillets I, et al. HIF-1Α is expressed in normoxic tissue and displays an organ ic-specific regulation under system in hypoxia[J]. FASEB J, 2001, 15(13):2445-2453.
[13] Sandau KB, Zhou J, Kietzmann T, et al. Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators nitric oxide and tumor necrosis factor-alpha in contrast to des-fe rroxamine and phenylarsine oxide[J]. J Biol Chem, 2001, 276(43):39805-39811.
[14] 丁虎, 刘晓然, 刘丹霞, 等. 急性运动诱导大鼠骨骼肌线粒体生物合成:H2O2参与介导PGC-1α转录[J]. 中国运动医学, 27(2):136-143.
[15] Hardie DG, Ross FA, Hawley SA. AMP-activated protein kinase:A target for drugs both ancient and modern[J]. Chem Biol, 2012, 19(10):1222-1236.
[16] Wang Y, Gao E, Tao L, et al. AMPK-activated protein ki-nase deficiency enhances myocardial ischemia/reperfusion in-jury but has minimal effect on the antioxidant/antinitrative protection of adiponectin[J]. Circulation, 2009, 119(6):835-844.
[17] Kim AS, Miller EJ, Wright TM, et al. A small AMPK acti-vator protects the heart against ischemia-reperfusion injury[J]. J Mol Cell Cardiol, 2011, 51(1):24-32.
[18] Mourorzis I, Giagourta I, Galanopoulos G, et al. Thyroid hormone improves the mechanical performance of the post-in-fa rcted diabetic myocardium:a response associated with up-regulation of Akt/mTOR and AMPK activation[J]. Metabolism, 2013, 62(10):1387-1393.
[19] Li L, Madu CO, Lu A, et al. HIF-1 alpha promotes a hypoxia-independent cell migration[J]. Open Biol J, 2010, 3:8-14.
[20] Yan BC, Park JH, Shin BN, et al. Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental ani-mal models of ischemic stroke[J]. PLoS One, 2013, 8(9):e74886.
[21] Ono Y, Sensui H, Sakamoto Y, et al. Knockdown of hypox-ia-inducible factor-1α by siRNA inhibits C2C12 myoblast differentiation[J]. J Cell Biochem, 2006, 98(3):642-649.
[22] Ogilvie M, Yu X, Nicolas-Metral V, et al. Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts[J]. Biol Chem, 2000, 275(50):39754-39761.