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Neuregulin reduces protein degradation in skeletal muscle in a PI3 kinase/Akt and MAP kinase dependent manner
Author(s) -
Hellyer Nathan J.,
Mantilla Carlos B.,
Sieck Gary C.
Publication year - 2010
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.24.1_supplement.1046.19
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , ly294002 , protein degradation , microbiology and biotechnology , protein kinase a , skeletal muscle , neuregulin 1 , chemistry , biology , signal transduction , kinase , endocrinology
Skeletal muscle growth is achieved by a net increase in muscle protein synthesis, decreased protein degradation or both. The Akt and mTOR signaling transduction pathways regulate both protein synthesis and degradation. We previously reported that the nerve‐derived growth factor neuregulin (NRG) increases muscle protein synthesis (~20%) in a PI3 kinase (PI3K)/Akt‐dependent manner. In the present study, we report that basal protein degradation in the diaphragm muscle is also significantly reduced by NRG treatment (23%). The NRG‐induced reduction of basal protein degradation is abrogated by pretreatment with inhibitors of PI3K (LY294002, 50 μM), mTOR (rapamycin, 100 nM) or MEK (PD98059, 50 μM). In fact, inhibition of any of these pathways alone is sufficient to increase basal protein degradation by greater than 30%. Importantly, NRG treatment nullifies the increase in protein degradation induced by PI3K or MEK inhibition, but not that induced by mTOR inhibition. Thus, unlike NRG effects on protein synthesis, the NRG‐induced decrease in protein degradation is abrogated not only by inhibition of the PI3K/Akt pathway, but also by inhibition of the MAP kinase. Based on these results, we suggest that both the PI3K/Akt and MAP kinase pathways are important for NRG effects on protein degradation, and that mTOR is a critical regulator of NRG effects on protein balance in skeletal muscle. Supported by NIH grant AR51173.