Focal Adhesion Kinase Signaling is Decreased 56 Days Following Spinal Cord Injury in Rat Gastrocnemius

Overview

Journal Spinal Cord

Specialty Neurology

Date 2015 Oct 21

PMID 26481700

Citations 7

Authors

Z A Graham

W Qin

L C Harlow

N H Ross

W A Bauman

P M Gallagher

C P Cardozo

Affiliations

Soon will be listed here.

Abstract

Study Design: Descriptive study.

Objectives: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius.

Setting: This study was conducted in Bronx, NY, USA.

Methods: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated.

Results: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or β1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or β1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI.

Conclusion: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.

Citing Articles

Effect of Mechanical Loading of Senescent Myoblasts on Their Myogenic Lineage Progression and Survival.

Moustogiannis A, Philippou A, Zevolis E, Taso O, Giannopoulos A, Chatzigeorgiou A Cells. 2022; 11(24).

PMID: 36552743 PMC: 9776690. DOI: 10.3390/cells11243979.

Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy.

Perovic D, Milavic M, Dokuzovic S, Krezic I, Gojkovic S, Vranes H Curr Issues Mol Biol. 2022; 44(5):1901-1927.

PMID: 35678659 PMC: 9164058. DOI: 10.3390/cimb44050130.

Master Regulators of Muscle Atrophy: Role of Costamere Components.

Gorza L, Sorge M, Secli L, Brancaccio M Cells. 2021; 10(1).

PMID: 33401549 PMC: 7823551. DOI: 10.3390/cells10010061.

A transcriptomic study of probenecid on injured spinal cords in mice.

Zhang Y, Wang S, Chen J, Hu J, Lu H PeerJ. 2020; 8:e8367.

PMID: 31921518 PMC: 6944129. DOI: 10.7717/peerj.8367.

Identification of serum exosomal microRNAs in acute spinal cord injured rats.

Ding S, Chen J, Wang S, Duan F, Chen Y, Shi Y Exp Biol Med (Maywood). 2019; 244(14):1149-1161.

PMID: 31450959 PMC: 6802156. DOI: 10.1177/1535370219872759.

References

Gan B, Yoo Y, Guan J . Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth. J Biol Chem. 2006; 281(49):37321-9. DOI: 10.1074/jbc.M605241200. View

Gordon S, Fluck M, Booth F . Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent. J Appl Physiol (1985). 2001; 90(3):1174-83; discussion 1165. DOI: 10.1152/jappl.2001.90.3.1174. View

Nolan K, Lacoste J, Parsons J . Regulated expression of focal adhesion kinase-related nonkinase, the autonomously expressed C-terminal domain of focal adhesion kinase. Mol Cell Biol. 1999; 19(9):6120-9. PMC: 84535. DOI: 10.1128/MCB.19.9.6120. View

Boppart M, Burkin D, Kaufman S . Activation of AKT signaling promotes cell growth and survival in α7β1 integrin-mediated alleviation of muscular dystrophy. Biochim Biophys Acta. 2011; 1812(4):439-46. PMC: 3046458. DOI: 10.1016/j.bbadis.2011.01.002. View

Wu Y, Zhao J, Zhao W, Pan J, Bauman W, Cardozo C . Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury. J Neurotrauma. 2012; 29(8):1663-75. PMC: 5364642. DOI: 10.1089/neu.2011.2203. View

Graham Z, Touchberry C, Gupte A, Bomhoff G, Geiger P, Gallagher P . Changes in α7β1 integrin signaling after eccentric exercise in heat-shocked rat soleus. Muscle Nerve. 2014; 51(4):562-8. DOI: 10.1002/mus.24324. View

Li R, Narici M, Erskine R, Seynnes O, Rittweger J, Pisot R . Costamere remodeling with muscle loading and unloading in healthy young men. J Anat. 2013; 223(5):525-36. PMC: 3916893. DOI: 10.1111/joa.12101. View

Roy R, Zhong H, Monti R, Vallance K, Edgerton V . Mechanical properties of the electrically silent adult rat soleus muscle. Muscle Nerve. 2002; 26(3):404-12. DOI: 10.1002/mus.10219. View

Mian M, Kang C, Lee S, Choi J, Bae S, Kim S . Cleavage of focal adhesion kinase is an early marker and modulator of oxidative stress-induced apoptosis. Chem Biol Interact. 2007; 171(1):57-66. DOI: 10.1016/j.cbi.2007.08.009. View

10.

Martineau L, Gardiner P . Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension. J Appl Physiol (1985). 2001; 91(2):693-702. DOI: 10.1152/jappl.2001.91.2.693. View

11.

Chen H, Appeddu P, Isoda H, Guan J . Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem. 1996; 271(42):26329-34. DOI: 10.1074/jbc.271.42.26329. View

12.

Roy R, Zhong H, Hodgson J, Grossman E, Siengthai B, Talmadge R . Influences of electromechanical events in defining skeletal muscle properties. Muscle Nerve. 2002; 26(2):238-51. DOI: 10.1002/mus.10189. View

13.

Torsoni A, Constancio S, Nadruz Jr W, Hanks S, Franchini K . Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes. Circ Res. 2003; 93(2):140-7. DOI: 10.1161/01.RES.0000081595.25297.1B. View

14.

Dreyer H, Glynn E, Lujan H, Fry C, DiCarlo S, Rasmussen B . Chronic paraplegia-induced muscle atrophy downregulates the mTOR/S6K1 signaling pathway. J Appl Physiol (1985). 2007; 104(1):27-33. PMC: 2715299. DOI: 10.1152/japplphysiol.00736.2007. View

15.

de Boer M, Selby A, Atherton P, Smith K, Seynnes O, Maganaris C . The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol. 2007; 585(Pt 1):241-51. PMC: 2375459. DOI: 10.1113/jphysiol.2007.142828. View

16.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

17.

Glass D . PI3 kinase regulation of skeletal muscle hypertrophy and atrophy. Curr Top Microbiol Immunol. 2010; 346:267-78. DOI: 10.1007/82_2010_78. View

18.

McClung J, Thompson R, Lowe L, Carson J . RhoA expression during recovery from skeletal muscle disuse. J Appl Physiol (1985). 2004; 96(4):1341-8. DOI: 10.1152/japplphysiol.01015.2003. View

19.

Durieux A, DAntona G, Desplanches D, Freyssenet D, Klossner S, Bottinelli R . Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype. J Physiol. 2009; 587(Pt 14):3703-17. PMC: 2742292. DOI: 10.1113/jphysiol.2009.171355. View

20.

Calalb M, Polte T, Hanks S . Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases. Mol Cell Biol. 1995; 15(2):954-63. PMC: 231984. DOI: 10.1128/MCB.15.2.954. View