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Neuregulin minimizes protein degradation induced by dexamethasone
Author(s) -
Argadine Heather,
Hellyer Nathan,
Mantilla Carlos,
Bailey Jeffrey,
Sieck Gary
Publication year - 2008
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.22.1_supplement.754.4
Subject(s) - eif4e , neuregulin 1 , pi3k/akt/mtor pathway , protein kinase b , neuregulin , protein degradation , protein biosynthesis , chemistry , microbiology and biotechnology , transcription factor , signal transduction , biology , translation (biology) , messenger rna , biochemistry , gene
Neuregulin (NRG) is part of the epidermal growth factor family of proteins. Previous studies have shown that NRG activates PI3K/Akt pathways, leading to regulation of protein synthesis via downstream regulation of translation initiators. The principal translation initiator involved in protein synthesis is probably eIF4E, and the principal transcription factor regulating protein degradation is FOXO. We hypothesized that NRG signaling involves activation of the PI3K/Akt pathway, thus leading to an increase in expression of eIF4E and a decrease in expression of FOXO. An increase in eIF4E expression increases protein synthesis, and a decrease in FOXO expression reduces protein degradation. In this study we used dexamethasone, a synthetic glucocorticoid, to induce atrophy and cause an imbalance between protein synthesis and degradation in L6 myotubes. As expected, we found that after 48 hours of treatment with 10–100nM dexamethasone, eIF4E expression decreased and FOXO expression increased in a dose‐dependent manner. We found that treatment with 200 ng/ml NRG increased eIF4E expression. When L6 cells were treated with both NRG and dexamethasone for 48 hours, NRG blunted the catabolic effects of dexamethasone, thus increasing eIF4E expression and decreasing FOXO expression. These results indicate that NRG promotes protein synthesis and prevents protein degradation. Supported by NIH grant AR51173.