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Differential Regulation of Ubiquitin ligases Atrogin‐1 and MuRF‐1 in Angiotensin II‐Mediated Skeletal Muscle Atrophy
Author(s) -
Yoshida Tadashi,
SemprunPrieto Laura,
Sukhanov Sergiy,
Delafontaine Patrick
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.600.27
Subject(s) - skeletal muscle , endocrinology , medicine , ubiquitin ligase , angiotensin ii , atrophy , ubiquitin , muscle atrophy , myocyte , chemistry , biology , receptor , biochemistry , gene
Advanced congestive heart failure is associated with activation of the renin‐angiotensin system and skeletal muscle atrophy. Angiotensin II (Ang II) infusion in mice produces cachexia secondarily to increase of muscle proteolysis mediated by two E3 ubiquitin ligase Atrogin‐1 and MuRF‐1, and also decreased levels of circulating and skeletal muscle IGF‐1. To determine mechanisms linking ubiquitin ligase expression and IGF‐1 signaling, time‐course dependent expression of Atrogin‐1, MuRF‐1, IGF‐1 and IGF‐1 receptor (IGF1R) was analyzed in skeletal muscles of Ang II infused mice. Expression of Atrogin‐1, MuRF‐1 and IGF1R were elevated one day after the initiation of Ang II‐infusion and were gradually decreased on day 4 and day 7. On the other hand, the expression of IGF‐1 was reduced on day 7. In skeletal muscles of mice overexpressing IGF‐1 specifically in skeletal muscle (MLC‐IGF‐1 mice), no significant reduction of skeletal muscle weight was observed after Ang II infusion and the basal and Ang II‐induced expression of Atrogin‐1 was significantly repressed. On the other hand, basal and Ang II‐induced expression of MuRF‐1 in skeletal muscles of MLC‐IGF‐1 mice was not different from WT animals. These data demonstrate that the IGF‐1 prevention of Ang II induced skeletal muscle atrophy is mediated via the ability of IGF‐1 to repress Atrogin‐1 expression, rather than MuRF‐1 expression. This work was supported by NIH Grant HL080682