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Muscle DRP‐1 and FIS‐1 Regulation by IL‐6 Signaling
Author(s) -
Fix Dennis,
VanderVeen Brandon N.,
Hardee Justin,
Carson James A.
Publication year - 2018
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.2018.32.1_supplement.864.13
Subject(s) - myogenesis , skeletal muscle , glycoprotein 130 , myocyte , microbiology and biotechnology , biology , mapk/erk pathway , stat3 , c2c12 , signal transduction , medicine , endocrinology , chemistry
The IL‐6 cytokine family signals through the ubiquitously expressed glycoprotein 130 (gp130) receptor to induce signal transducer and activator of transcription 3 (STAT3) and extracellular signal‐regulated kinase 1/2 (ERK1/2). Evidence suggests that IL‐6 can negatively regulate muscle mitochondrial quality control and disrupt muscle oxidative metabolism. Mitochondrial fission is a critical component of skeletal muscle mitochondria maintenance and oxidative metabolism, which is regulated impart by the expression of FIS‐1 and DRP‐1 proteins. The purpose of this study is to examine muscle DRP‐1 and FIS‐1 expression by IL‐6 signaling. Methods Fully differentiated C2C12 myotubes were treated with 100ng of IL‐6 for 24 hours in the presence of gp130siRNA, C188‐9 (STAT3 inhibitor), or PD98059 (ERK1/2 inhibitor). Additionally, male C57BL/6 (B6) and muscle specific gp130 knockout mice (KO) were electroporated in the quadriceps muscles with 50ng of IL‐6 and monitored for two weeks. Results IL‐6 induced DRP‐1 and FIS‐1 expression in myotubes and skeletal muscle. Knock down of gp130 in myotubes and KO in skeletal muscle inhibited the IL‐6 induction of DRP‐1 and FIS‐1. STAT3 inhibition in myotubes did not alter IL‐6 induced DRP‐1 and FIS‐1 expression, while ERK 1/2 inhibited the IL‐6 induction. Collectively, these results provide evidence for skeletal muscle mitochondrial fission regualtion through an IL‐6/gp130/ERK 1/2 signaling axis. Support or Funding Information This work was supported by National Institutes of Health grant # NCI‐R01CA121249 (JAC). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .