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TWEAK causes cell death in cultured primary myotubes (LB816)
Author(s) -
Ogura Yuji,
Kumar Ashok
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.lb816
Subject(s) - myogenesis , tumor necrosis factor alpha , apoptosis , biology , proinflammatory cytokine , microbiology and biotechnology , cytokine , programmed cell death , viability assay , tunel assay , myocyte , endocrinology , immunology , inflammation , biochemistry
Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine belonging to TNF super family. TWEAK produces a variety of cellular responses through binding to fibroblast growth factor inducible 14 (Fn14), a member of TNF receptor superfamily. Although Fn14 lacks a death domain, TWEAK has been found to induce apoptosis in some cell types by perturbing the activity of certain pathway such as TNFα‐TNF receptor signaling. TWEAK is also known to regulate proliferation and differentiation of myogenic cells. We have previously reported that TWEAK‐Fn14 system causes muscle atrophy both in vitro and in vivo. Moreover, it has been reported that TWEAK mediates muscle atrophy in disuse conditions such as denervation. However, it remains unknown whether TWEAK can affect the viability of muscle cells. To address this issue, we have studied the effects of recombinant TWEAK protein on survival of cultured mouse primary myotubes. Our results demonstrate that TWEAK reduces myotube viability in a dose‐dependent manner evident by increased levels of lactate dehydrogenase (LDH) in culture supernatants. TWEAK also increased the number of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)‐positive nuclei in cultured myotubes. Furthermore, we have found that the levels of cleaved poly ADP ribose polymerase (PARP) are increased upon treatment with TWEAK for 48 and 72h. These results provide initial evidence that in addition to causing atrophy, TWEAK can also diminish skeletal muscle mass by affecting the survival of myofibers in different catabolic conditions. Grant Funding Source : Supported by NIH RO1AG029623