SS-31 attenuates TNF-α induced cytokine release from C2C12 myotubes

Abstract

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.

Chemokine (C‐X‐C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells

“…Therefore, it is possible that the contraction‐induced increase in Cxcl1 expression is also mediated by NF‐κB signalling. Supplementation with tumour necrosis factor‐α, a potent NF‐κB activator, increases the CXCL1 protein level in the culture media of C2C12 myotubes, astrocytes and endothelial cells . This increase in the CXCL1 protein level is inhibited by BAY11‐7082, which agrees with our results.…”

17-(Allylamino)-17demethoxygeldanamycin reduces Endoplasmic Reticulum (ER) stress-induced mitochondrial dysfunction in C2C12 myotubes

“…the atrogenes Atrogin-1 and MuRF-1 , and NF-κB activation. We have previously demonstrated the use of IkappaBalpha (IκBα) degradation as a sensitive way of indirectly assessing nuclear factor kappa B (NF-κB) activity in C2C12 myotubes, [27]. Surprisingly, in the current experiments, we observed no Tunicamycin-induced changes in Atrogin-1 or MuRF-1 gene expression levels.…”

Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

“…We 33 34 and others 35 36 have recently reported that pharmacological application of the mitochondria-targeted SS31 tetrapeptide can attenuate mitochondrial superoxide production in intact mitochondria of skeletal muscle fibers. This pharmacological approach complements genetic approaches, including those using targeted overexpression of the human catalase gene to mitochondria (MCat mice) 2 23 .…”