PI3 Kinase Regulation of Neural Regeneration and Muscle Hypertrophy After Spinal Cord Injury

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2011 Jul 2

PMID 21720761

Citations 20

Authors

Tengfei Zhao

Yiying Qi

Yan Li

Kan Xu

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) is a serious neurotrauma that can lead to life-long disability; to date, no suitable therapeutic strategy exists. Axons do not regenerate after SCI in adult mammals and loss of skeletal muscle mass occurs very rapidly after SCI. Promotion of neurite growth through improving the extracellular environment allows only a limited degree of axon regeneration. The phosphatidylinositol-3 kinase (PI3K)/Akt pathway and its downstream targets ("mammalian target of rapamycin," mTOR, and glycogen synthase kinase-3), which regulate cell growth and proliferation in many tissues, have been suggested to play an important role in regulation of the intrinsic axonal regeneration and muscle hypertrophy. This review is focused on recent progress in our understanding of the PI3K pathway in the modulation of axonal regeneration and muscle hypertrophy after SCI.

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References

Fingar D, Blenis J . Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene. 2004; 23(18):3151-71. DOI: 10.1038/sj.onc.1207542. View

Leger B, Vergani L, Soraru G, Hespel P, Derave W, Gobelet C . Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB J. 2006; 20(3):583-5. DOI: 10.1096/fj.05-5249fje. View

Kim W, Zhou F, Zhou J, Yokota Y, Wang Y, Yoshimura T . Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth. Neuron. 2006; 52(6):981-96. PMC: 4167845. DOI: 10.1016/j.neuron.2006.10.031. View

Coghlan M, Culbert A, Cross D, Corcoran S, YATES J, Pearce N . Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol. 2000; 7(10):793-803. DOI: 10.1016/s1074-5521(00)00025-9. View

Rommel C, Bodine S, Clarke B, Rossman R, Nunez L, Stitt T . Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001; 3(11):1009-13. DOI: 10.1038/ncb1101-1009. View

Rhoads R . Signal transduction pathways that regulate eukaryotic protein synthesis. J Biol Chem. 1999; 274(43):30337-40. DOI: 10.1074/jbc.274.43.30337. View

Garshick E, Kelley A, Cohen S, Garrison A, Tun C, Gagnon D . A prospective assessment of mortality in chronic spinal cord injury. Spinal Cord. 2005; 43(7):408-16. PMC: 1298182. DOI: 10.1038/sj.sc.3101729. View

Gingras A, Raught B, Sonenberg N . Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001; 15(7):807-26. DOI: 10.1101/gad.887201. View

Kandarian S, Jackman R . Intracellular signaling during skeletal muscle atrophy. Muscle Nerve. 2005; 33(2):155-65. DOI: 10.1002/mus.20442. View

10.

Christie K, Webber C, Martinez J, Singh B, Zochodne D . PTEN inhibition to facilitate intrinsic regenerative outgrowth of adult peripheral axons. J Neurosci. 2010; 30(27):9306-15. PMC: 6632469. DOI: 10.1523/JNEUROSCI.6271-09.2010. View

11.

Woodgett J . Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J. 1990; 9(8):2431-8. PMC: 552268. DOI: 10.1002/j.1460-2075.1990.tb07419.x. View

12.

Kimball S, Farrell P, Jefferson L . Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol (1985). 2002; 93(3):1168-80. DOI: 10.1152/japplphysiol.00221.2002. View

13.

Leger B, Senese R, Al-Khodairy A, Deriaz O, Gobelet C, Giacobino J . Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. Muscle Nerve. 2009; 40(1):69-78. DOI: 10.1002/mus.21293. View

14.

Ladner K, Caligiuri M, Guttridge D . Tumor necrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products. J Biol Chem. 2002; 278(4):2294-303. DOI: 10.1074/jbc.M207129200. View

15.

Kim D, Sarbassov D, Ali S, Latek R, Guntur K, Erdjument-Bromage H . GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell. 2003; 11(4):895-904. DOI: 10.1016/s1097-2765(03)00114-x. View

16.

Dudley G, Castro M, Rogers S, Apple Jr D . A simple means of increasing muscle size after spinal cord injury: a pilot study. Eur J Appl Physiol Occup Physiol. 1999; 80(4):394-6. DOI: 10.1007/s004210050609. View

17.

Mao X, Zeng X, Wang J, Qiao S . Leucine promotes leptin receptor expression in mouse C2C12 myotubes through the mTOR pathway. Mol Biol Rep. 2010; 38(5):3201-6. DOI: 10.1007/s11033-010-9992-6. View

18.

Liu M, Bose P, Walter G, Thompson F, Vandenborne K . A longitudinal study of skeletal muscle following spinal cord injury and locomotor training. Spinal Cord. 2008; 46(7):488-93. DOI: 10.1038/sj.sc.3102169. View

19.

Kraus J, Greenland S . Survival from spinal cord injury. J Chronic Dis. 1983; 36(3):297-8. DOI: 10.1016/0021-9681(83)90065-6. View

20.

Fitch M, Silver J . CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol. 2007; 209(2):294-301. PMC: 2268907. DOI: 10.1016/j.expneurol.2007.05.014. View