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Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin‐1
Author(s) -
Léger Bertrand,
Vergani Lodovica,
Sorarù Gianni,
Hespel Peter,
Derave Wim,
Gobelet Charles,
D'Ascenzio Carla,
Angelini Corrado,
Russell Aaron P.
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/fj.05-5249fje
Subject(s) - protein kinase b , muscle atrophy , amyotrophic lateral sclerosis , atrophy , p70 s6 kinase 1 , skeletal muscle , foxo1 , medicine , endocrinology , biology , foxo3 , signal transduction , microbiology and biotechnology , disease
The molecular mechanisms influencing muscle atrophy in humans are poorly understood. Atrogin‐1 and MuRF1, two ubiquitin E3‐ligases, mediate rodent and cell muscle atrophy and are suggested to be regulated by an Akt/Forkhead (FKHR) signaling pathway. Here we investigated the expression of atrogin‐1, MuRF1, and the activity of Akt and its catabolic (FKHR and FKHRL1) and anabolic (p70 s6k and GSK‐3?) targets in human skeletal muscle atrophy. The muscle atrophy model used was amyotrophic lateral sclerosis (ALS). All measurements were performed in biopsies from 22 ALS patients and 16 healthy controls as well as in G93A ALS mice. ALS patients had a significant increase in atrogin‐1 mRNA and protein content, which was associated with a decrease in Akt activity. There was no difference in the mRNA and protein content of FKHR, FKHRL1, p70 s6k , and GSK‐3?. Similar observations were made in the G93A ALS mice. Human skeletal muscle atrophy, as seen in the ALS model, is associated with an increase in atrogin‐1 and a decrease in Akt. The transcriptional regulation of human atrogin‐1 may be controlled by an Akt‐mediated transcription factor other than FKHR or via another signaling pathway.