Premium
Myopathy and altered gastrocnemius and cardiac mTOR signaling in muscle‐specific LKB1 knockout mice
Author(s) -
Malan Brandon B.,
Mongillo Anthony D.,
Thomson David M.
Publication year - 2009
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.23.1_supplement.782.6
Subject(s) - pi3k/akt/mtor pathway , skeletal muscle , p70 s6 kinase 1 , medicine , endocrinology , phosphorylation , ampk , gastrocnemius muscle , muscle hypertrophy , muscle atrophy , knockout mouse , cardiac muscle , protein kinase b , amp activated protein kinase , biology , protein kinase a , signal transduction , microbiology and biotechnology , receptor
LKB1/AMP‐activated protein kinase (AMPK) activity is known to inhibit protein synthesis in skeletal and cardiac muscle in part through inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. However, the role of LKB1 in regulating heart and skeletal muscle size is not well understood. We have observed a progressive, age‐related myopathic phenotype in muscle specific LKB1 knockout (MLKB1‐KO) mice, which is associated with concurrent skeletal muscle atrophy and cardiac hypertrophy. The purpose of this study was to compare the phosphorylation of various components of the mTOR signaling pathway in atrophic gastrocnemius and hypertrophic heart muscles from MLKB1‐KO and littermate control (C) mice. Phosphorylation of mTOR, 4E‐BP1, and p70S6k were 65.6%, 20.3%, and 70.0% lower in MLKB1‐KO gastrocnemius muscles, respectively. Conversely, mTOR and S6k phosphorylation were 44.5% and 76.1% greater, respectively, in MLKB1‐KO hearts, although the difference was not significant for p70S6k (p = 0.19). No difference between genotypes was observed for 4E‐BP1 phosphorylation in the heart. Taken together, these findings indicate that alterations in mTOR signaling may contribute to cardiac hypertrophy and skeletal muscle atrophy in the MLKB1‐KO mouse. This study was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR‐051928.