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Mitochondrial superoxide mediates TNF‐α‐induced myokine release from C2C12 myotubes (1153.4)
Author(s) -
Lightfoot Adam,
Sakellariou Giorgos,
Nye Gareth,
McArdle Francis,
Jackson Malcolm,
Griffiths Richard,
McArdle Anne
Publication year - 2014
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.28.1_supplement.1153.4
Subject(s) - myokine , superoxide , skeletal muscle , myogenesis , reactive oxygen species , chemistry , tumor necrosis factor alpha , c2c12 , myocyte , mitochondrial ros , mitochondrion , medicine , endocrinology , microbiology and biotechnology , biochemistry , biology , enzyme
TNF‐α is a key inflammatory mediator and is proposed to induce transcriptional responses via the generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the role of mitochondrial superoxide generation in TNF‐α ‐ induced generation of myokines by skeletal muscle. Significant elevation in the release of IL‐6 (control untreated: 20.1pg/ml ± 2.3; TNF‐α treated: 73.8pg/ml ± 9.3), CCL2/MCP‐1 (980pg/ml ± 74.8; 31194pg/ml ± 5409), CCL5/RANTES (22.4pg/ml ± 2.09; 604pg/ml ± 93.4) and CXCL1/KC (236pg/ml ± 32.6; 3477pg/ml ± 383) and in superoxide, localised to the mitochondria were seen in response to TNF‐α treatment of muscle cells and this was associated with activation of NFκB. The TNF‐α mediated changes in superoxide, activation of NFκB and increased release of myokines were attenuated following pre‐treatment with the mitochondria targeted antioxidant, SS‐31 peptide (IL‐6, 11.9pg/ml ± 1.83; MCP‐1, 11322pg/ml ± 1124; RANTES, 252pg/ml ± 51.4; KC, 1166pg/ml ± 204) indicating that the ability of TNF‐α to induce myokine release is mediated through mitochondrial superoxide, which is, at least in part, associated with activation of the redox sensitive transcription factor NFκB. These novel findings provide evidence that targeting mitochondrial ROS could provide a potential for therapy for inflammatory myopathies. The authors thank the Medical Research Council and National Institute on Aging (grant AG‐020591) for their generous financial support and Dr M.B Reid (University of Kentucky Center for Muscle Biology) for the kind gift of the SS‐31 peptide.