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IL‐1β Induces Catabolic Signaling in C2C12 Myotubes
Author(s) -
Li Wei,
Moylan Jennifer S,
Smith Jeffrey D,
Smith Jacqueline L,
Reid Michael B
Publication year - 2006
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.20.4.a802-a
Subject(s) - myogenesis , wasting , cachexia , ubiquitin , myostatin , inflammation , catabolism , signal transduction , p38 mitogen activated protein kinases , tumor necrosis factor alpha , endocrinology , downregulation and upregulation , proinflammatory cytokine , skeletal muscle , cancer research , medicine , chemistry , microbiology and biotechnology , biology , mapk/erk pathway , gene , cancer , biochemistry , metabolism
Debilitating chronic disease such as congestive heart failure, cancer, COPD and AIDS often leads to severe muscle wasting or cachexia. Inflammatory cytokines are important mediators of cachexia. Among these, TNFα is the most well studied. The contribution of other inflammatory cytokines is less understood. In this study we show that, similar to TNFα, IL‐1β activates catabolic signaling that leads to muscle wasting. We show IL‐1β activation of ubiquitins. uba and ubb gene expression increased 1.3 fold at 24 hours IL‐1β treatment. ubc gene expression increased 1.4 fold 2 hours following treatment. We also show that IL‐1β upregulates expression of the muscle specific ubiquitin ligases, Atrogin1/MAFbx and MuRF1, 4 and 1.7 fold respectively 2 hours after treatment. We have begun to define the signaling pathways that regulate these ubiquitin conjugating enzymes. We show that IL‐1β induced Atrogin expression is at least partially dependent on p38 MAPK, since p38 inhibitor SB203580 blunts the Atrogin response. However, MuRF1 expression is unaffected by the SB203580. Instead, it is most likely regulated by NFkB signaling. We have shown that IL‐1β causes degradation of IkB 15 mins after treatment, while NFkB DNA binding activity increases after 30 mins. These data suggest a mechanism whereby IL‐1β may contribute to the muscle wasting associated with chronic disease. Suported by NIH grant HL59878