Research Article

Kynurenine, a Tryptophan Metabolite That Increases with Age, Induces Muscle Atrophy and Lipid Peroxidation

Figure 1

Increased measures of oxidative stress, reduction in muscle fiber size, and reduced muscle strength after KYN treatment in vitro and in vivo. (a) H2O2 levels were significantly increased in mouse C2C12 myoblasts after 24 hours of 1 μM and 10 μM KYN treatment compared to VEH treatment. /group. (b) H2O2 levels in human primary myoblasts were increased significantly after 24 hours of 10 μM KYN treatment compared to VEH treatment. /group. (c) After 4 weeks of treatment with KYN or VEH, young female mice did not have a reduction in quadriceps mass compared to body mass. (d, e) Quadriceps fiber size was significantly reduced with KYN treatment in young female mice, visualized with laminin staining (scale bar 100 μm). (f, g) Young female mice treated with KYN had a significant increase in lipid peroxidation, measured by 4HNE staining, when compared to young VEH mice or old VEH mice. (h) Changes in the expression of muscle structural protein genes in quadriceps muscles from young female mice treated with KYN compared to young VEH. (i) Young female mice lost significant peak muscle strength after 4 weeks of KYN treatment. /group for C-I. Data are presented as . , , and . Representative muscle fibers are marked with stars in d and g.
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
(i)