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IGF‐1/Akt/mTOR‐GSK‐3β signaling in skeletal muscle in human heart failure
Author(s) -
Toth Michael J.,
Ward Kimberly,
Velden Jos,
Miller Mark S.,
VanBuren Peter,
LeWinter Martin M.,
Ades Philip A.
Publication year - 2011
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.25.1_supplement.1059.12
Subject(s) - protein kinase b , phosphorylation , pi3k/akt/mtor pathway , myosin , skeletal muscle , myofibril , p70 s6 kinase 1 , medicine , endocrinology , chemistry , signal transduction , biology , biochemistry
Patients with chronic heart failure (HF) lose skeletal muscle mass and function during the course of the disease. The present study examined whether IGF‐1 expression and phosphorylation of downstream signaling molecules are altered under rested, postabsorptive conditions in skeletal muscle of HF patients (n=11) vs. controls (n=11). IGF‐1 expression was similar between patients and controls. Despite this, HF patients were characterized by reduced levels of phospho‐Akt/Akt (S473; −43%; P<0.05), whereas no differences were found in Akt protein content or phospho‐ or total protein content of mTOR (S2448), GSK‐3β (S9), eIF4E‐BP (T37/46), p70 S6 kinase (T389) or eIF2Bε (S540). Reduced phospho‐Akt/Akt levels were related to decreased muscle myosin protein content (r=0.602; P<0.02). Considering the potential role for phosphorylation of Akt on S473 for directing its effects on protein breakdown via FOXO, we evaluated atrogene expression and indices of myofibrillar protein breakdown in a sub‐set of volunteers. No group differences were noted, however, in either atrogene expression or protein breakdown markers. Because patients and controls were similar for age, muscle mass and physical activity level, we ascribe the observed alterations in Akt phosphorylation and its relationship to myosin protein content, a molecular marker of muscle size and function, to the unique effects of the HF syndrome.