SS-31 attenuates TNF-α induced cytokine release from C2C12 myotubes.
TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the mitochondrial generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the effect of TNF-α on the production of myokines by skeletal muscle. Significant increases were seen in the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of cytokines by muscle cells. An increase was also seen in superoxide in response to treatment with TNF-α, which was localised to the mitochondria and this was also associated with activation of NF-κB. The changes in superoxide, activation of NF-kB and release of myokines were attenuated following pre-treatment with SS-31 peptide indicating that the ability of TNF-α to induce myokine release may be mediated through mitochondrial superoxide, which is, at least in part, associated with activation of the redox sensitive transcription factor NF-kB.
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Adam P
AP
Lightfoot
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Giorgos K
GK
Sakellariou
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Gareth A
GA
Nye
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Francis
F
McArdle
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Malcolm J
MJ
Jackson
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom.
Richard D
RD
Griffiths
MRC-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, United Kingdom. Electronic address: mdcr02@liv.ac.uk.
Anne
A
McArdle
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D015398:Signal Transduction; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016166:Free Radical Scavengers; D015850:Interleukin-6; D016328:NF-kappa B; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; C577686:interleukin-6, mouse; D013481:Superoxides; D020126:Brefeldin A
C2C12; Myokine; Skeletal muscle; Superoxide; TNF