Acute Resistance Exercise and Training Reduce Desmin Phosphorylation at Serine 31 in Human Skeletal Muscle, Making the Protein Less Prone to Cleavage

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 14

PMID 39543356

Authors

Daniel Jacko

Kirill Schaaf

Thorben Aussieker

Lukas Masur

Jonas Zacher

Kathe Bersiner

Wilhelm Bloch

Sebastian Gehlert

Affiliations

Soon will be listed here.

Abstract

Desmin intermediate filaments play a crucial role in stress transmission and mechano-protection. The loss of its integrity triggers myofibril breakdown and muscle atrophy for which desmin phosphorylation (Des) is a priming factor. We investigated whether eccentric accentuated resistance exercise (RE) influences the regulation of Des, effecting its susceptibility to cleavage. Ten healthy persons performed 14 RE-sessions (2 per week). Muscle biopsies were collected in both untrained and trained conditions at rest (pre 1, pre 14) and one hour after RE (post 1, post 14). Western blotting and immunohistochemistry were utilized to assess desmin content, phosphorylation at several sites and susceptibility to cleavage. In untrained condition (pre 1, post 1), RE induced dephosphorylation of serin 31 and 60. Trained muscle exhibited more pronounced dephosphorylation at Serin 31 post-RE. Dephosphorylation was accompanied by reduced susceptibility of desmin to cleavage. Additionally, training increased total desmin content, upregulated baseline serine 31 phosphorylation and attenuated pDes at serine 60 and threonine 17. Our findings suggest that acute and repeated RE changes the phosphorylation pattern of desmin and its susceptibility to cleavage, highlighting Des as an adaptive mechanism in skeletal muscle, contributing to the proteostatic regulation in response to recurring stress.

References

Murgia M, Nogara L, Baraldo M, Reggiani C, Mann M, Schiaffino S . Protein profile of fiber types in human skeletal muscle: a single-fiber proteomics study. Skelet Muscle. 2021; 11(1):24. PMC: 8561870. DOI: 10.1186/s13395-021-00279-0. View

Ogasawara R, Kobayashi K, Tsutaki A, Lee K, Abe T, Fujita S . mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle. J Appl Physiol (1985). 2013; 114(7):934-40. DOI: 10.1152/japplphysiol.01161.2012. View

Komulainen J, Takala T, Kuipers H, Hesselink M . The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions. Pflugers Arch. 1998; 436(5):735-41. DOI: 10.1007/s004240050696. View

Mittal B, Sanger J, Sanger J . Visualization of intermediate filaments in living cells using fluorescently labeled desmin. Cell Motil Cytoskeleton. 1989; 12(3):127-38. DOI: 10.1002/cm.970120302. View

Hart G . Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. Annu Rev Biochem. 1997; 66:315-35. DOI: 10.1146/annurev.biochem.66.1.315. View

Agnetti G, Herrmann H, Cohen S . New roles for desmin in the maintenance of muscle homeostasis. FEBS J. 2021; 289(10):2755-2770. DOI: 10.1111/febs.15864. View

Hughes D, Ellefsen S, Baar K . Adaptations to Endurance and Strength Training. Cold Spring Harb Perspect Med. 2017; 8(6). PMC: 5983157. DOI: 10.1101/cshperspect.a029769. View

Herrmann H, Aebi U . Intermediate Filaments: Structure and Assembly. Cold Spring Harb Perspect Biol. 2016; 8(11). PMC: 5088526. DOI: 10.1101/cshperspect.a018242. View

Joanne P, Hovhannisyan Y, Bencze M, Daher M, Parlakian A, Toutirais G . Absence of Desmin Results in Impaired Adaptive Response to Mechanical Overloading of Skeletal Muscle. Front Cell Dev Biol. 2021; 9:662133. PMC: 8320001. DOI: 10.3389/fcell.2021.662133. View

10.

Sakamoto K, Aschenbach W, Hirshman M, Goodyear L . Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am J Physiol Endocrinol Metab. 2003; 285(5):E1081-8. DOI: 10.1152/ajpendo.00228.2003. View

11.

Mylonas R, Potts A, Waridel P, Barblan J, Conde Rubio M, Widmann C . A Database of Accurate Electrophoretic Migration Patterns for Human Proteins. J Mol Biol. 2022; 435(4):167933. DOI: 10.1016/j.jmb.2022.167933. View

12.

Stozer A, Vodopivc P, Krizancic Bombek L . Pathophysiology of exercise-induced muscle damage and its structural, functional, metabolic, and clinical consequences. Physiol Res. 2020; 69(4):565-598. PMC: 8549894. DOI: 10.33549/physiolres.934371. View

13.

Kawajiri A, Yasui Y, Goto H, Tatsuka M, Takahashi M, Nagata K . Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase. Mol Biol Cell. 2003; 14(4):1489-500. PMC: 153117. DOI: 10.1091/mbc.e02-09-0612. View

14.

Baron C, Jacobsen S, Purslow P . Cleavage of desmin by cysteine proteases: Calpains and cathepsin B. Meat Sci. 2011; 68(3):447-56. DOI: 10.1016/j.meatsci.2004.03.019. View

15.

Barash I, Peters D, Friden J, Lutz G, Lieber R . Desmin cytoskeletal modifications after a bout of eccentric exercise in the rat. Am J Physiol Regul Integr Comp Physiol. 2002; 283(4):R958-63. DOI: 10.1152/ajpregu.00185.2002. View

16.

Amin H, Vachris J, Hamilton A, Steuerwald N, Howden R, Arthur S . GSK3β inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running. J Physiol Sci. 2013; 64(1):1-11. PMC: 10717853. DOI: 10.1007/s12576-013-0284-5. View

17.

Hurst C, Robinson S, Witham M, Dodds R, Granic A, Buckland C . Resistance exercise as a treatment for sarcopenia: prescription and delivery. Age Ageing. 2022; 51(2). PMC: 8840798. DOI: 10.1093/ageing/afac003. View

18.

Nelson W, Traub P . Proteolysis of vimentin and desmin by the Ca2+-activated proteinase specific for these intermediate filament proteins. Mol Cell Biol. 1983; 3(6):1146-56. PMC: 368644. DOI: 10.1128/mcb.3.6.1146-1156.1983. View

19.

Markuns J, Wojtaszewski J, Goodyear L . Insulin and exercise decrease glycogen synthase kinase-3 activity by different mechanisms in rat skeletal muscle. J Biol Chem. 1999; 274(35):24896-900. DOI: 10.1074/jbc.274.35.24896. View

20.

Giovarelli M, Zecchini S, Martini E, Garre M, Barozzi S, Ripolone M . Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle. Cell Death Differ. 2020; 27(8):2383-2401. PMC: 7370230. DOI: 10.1038/s41418-020-0510-7. View