The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity
J. Clin. Invest. Jun-ichi Hanai, et al. 117:3940 doi:10.1172/JCI32741 [
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Figure 4Myotubes from
atrogin-1 null (–/–) mice are resistant to lovastatin-induced damage.
(
A) Atrogin-1 protein expression is absent in
atrogin-1 null (–/–) myotubes. Myoblasts derived from
atrogin-1 knockout mice (–/–) and corresponding wild type (+/+) littermates were differentiated into myotubes. Cultures were stimulated to express atrogin-1 with dexamethasone (5 μM) or infected with constitutively active FoxO3- or GFP-expressing adenovirus (
45). Atrogin-1 expression was detected by Western blotting as in Figure
3. (
B) Myotubes from
atrogin-1 null (–/–) and wild-type (+/+) mice were treated with lovastatin at the indicated concentrations for 48 hours. Myotube morphology was examined, and diameter was measured. Original magnification, ×100.