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Exosomal Signaling by Skeletal Muscle: Role in Neuromuscular Ageing
Author(s) -
Hemmings Kay,
Girithananda Aarthi,
Robertson Rebecca,
Pugh Jamie,
Scalabrin Mattia,
Mora Silvia,
McArdle Anne
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.536.20
Subject(s) - proteostasis , exosome , heat shock protein , microvesicles , microbiology and biotechnology , skeletal muscle , contraction (grammar) , hsp70 , biology , chemistry , muscle contraction , myocyte , medicine , endocrinology , biochemistry , microrna , gene
Muscle mass and function are reduced with age in mammals and this is associated with disrupted neuromuscular interactions. Skeletal muscle mounts a robust stress response to contractions by the increased expression of Heat Shock Proteins (HSPs), which facilitate muscle remodelling, promote protein folding and clearance of damaged proteins. In contrast, other tissues, including neuronal cells are unable to mount a stress response. It has been proposed that HSPs may be transferred from one cell type to another in exosomes to maintain proteostasis in the recipient cells. Further, HSP generation by muscle following contractions is attenuated in old mice and humans. We hypothesise that this inability of muscles of old mice to produce HSPs in response to contractions results in altered exosomal HSP transfer, and therefore a failure to maintain proteostasis in neighbouring cells including motor neurons, with subsequent neuronal and muscle degeneration (1). Single muscle fibres were isolated from flexor digitorum bravis (FDB) muscles of adult (6–12 month) mice, and initiated to contract using a non‐damaging electrical stimulation protocol. Media was collected at time points up to 24hrs, and exosomes were purified from the media using ultracentrifugation approaches. NanoSight analysis was used to characterize and quantify the exosomes, and HSP content analysed by western blotting. Data demonstrated that there was a significant (2–3 fold) increase in exosome release by muscle fibres of adult mice following contraction compared with non‐stimulated controls, and that the exosomal HSP content was also increased. For example, at 4hrs post contraction, there was no increase in HSP25 content of exosomes but a 2 fold increase in HSP60 was detected at this time point compared with non‐stimulated controls. Preliminary data also showed that there was a 3.5 fold increase in HSP25 exosomal content at 24hrs post stimulation. Additional data demonstrated the potential uptake of exosomes labelled with lipophilic carbocyanine fluorescent dye by immortalized neuronal cells. Additional studies will also examine the effect of age on exosome production by muscle fibres, including HSP content and neuronal uptake, by comparison with muscle from CuZn superoxide dismutase (CuZnSOD) null mice, a model of accelerated muscle ageing. Support or Funding Information With thanks to National Institute of Ageing (AG051442), the Physiological Society (summer studentship awarded to RR) and the University of Liverpool for their generous support. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .