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Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1

Leger, Bertrand, Vergani, Lodovica, Soraru, Gianni, Hespel, Peter, Derave, Wim, Gobelet, Charles, D`Ascenzio, Carla, Angelini, Corrado and Russell, Aaron 2006, Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1, The FASEB journal : official publication of the Federation of American Societies for experimental biology, vol. 20, no. 3, pp. 583-585, doi: 10.1096/fj.05-5249fje.

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Title Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1
Author(s) Leger, Bertrand
Vergani, Lodovica
Soraru, Gianni
Hespel, Peter
Derave, Wim
Gobelet, Charles
D`Ascenzio, Carla
Angelini, Corrado
Russell, AaronORCID iD for Russell, Aaron orcid.org/0000-0002-7323-9501
Journal name The FASEB journal : official publication of the Federation of American Societies for experimental biology
Volume number 20
Issue number 3
Start page 583
End page 585
Publisher Federation of American Societies for Experimental Biology
Place of publication Bethesda, Md.
Publication date 2006-03
ISSN 0892-6638
1530-6860
Keyword(s) E3 ligase
neurodegenerative disease
Summary 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 (p70s6k and GSK-3β) 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, p70s6k, and GSK-3β. 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.
Language eng
DOI 10.1096/fj.05-5249fje
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, FASEB
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006621

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