Avenanthramides attenuate inflammation and atrophy in muscle cells

Background: Chronic inflammation is an important etiologic mechanism for muscle atrophy. Oat-derived phytochemical avenanthramides(AVAs) have been shown to suppress inflammatory responses in human clinical studies and in several cell lines in vitro, but their role in skeletal muscle is unclear. The aim of this study was to investigate whether AVA treatment can prevent tumor necrosis factor(TNF)-a-induced muscle fiber atrophy in C2 C12 cells.Methods: We treated 70% confluent cells for 24 h with AVA. Then, TNF-a was added to cell-cultured medium. Subsequently, cells were harvested at different time points. The cells were examined using various biochemical techniques for measuring protein, messenger RNA levels,nuclear binding activity, and viability. Fluorescence microscope was used for analysis of the myotube morphology.Results: Cells treated with TNF-a significantly increased nuclear factor k B activation, indicated by a marked decrease of Ik B(p < 0.05) and a6.6-fold increase in p65-DNA binding(p < 0.01); however, 30 mmol of AVA-A,-B, and-C treatment reduced the binding by 33%, 18%, and19%(p < 0.01), respectively, compared with cells treated with TNF-a without AVA. The interleukin-6 level increased by 2.5 fold(p < 0.01)with TNF-a, but decreased by 24%, 32%, and 28%(p < 0.01), respectively, with AVA-A,-B, and-C. The interleukin-1 b level also showed a47% increase with TNF-a(p < 0.01), whereas this increment was abolished in all AVA-treated cells. Reactive oxygen species production was1.3-fold higher in the TNF-a-treated group(p < 0.01) but not in the TNF-a + AVAs groups. Messenger RNA levels of muscle-specific E3 ubiquitin ligase atrogin-1 increased 23% in TNF-a vs. control(p < 0.05) but was decreased by 46%, 34%, and 53%(p < 0.01), respectively, with treatment of AVA-A,-B, and-C. Moreover, TNF-a treatment increased the muscle RING finger 1 messenger RNA level by 76%(p < 0.01);this change was abolished by AVAs. Cells treated with TNF-a demonstrated a reduced proliferation compared with control cells(p < 0.01), but this effect was not seen in TNF-a + AVAs cells. The diameter of the C2 C12 myotube decreased by 28%(p < 0.01) with TNF-a, whereas it showed no change when AVAs were included in the cell media.Conclusion: These results indicated that AVAs can reduce proinflammatory cytokine and reactive oxygen species production and ameliorate TNF-a-induced myotube atrophy in muscle cells.

Role of PGC-1αin muscle function and aging

This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.

The role of mitochondria in redox signaling of muscle homeostasis

In the past,contraction-induced production of reactive oxygen species(ROS)has been implicated in oxidative stress to skeletal muscle.As research advances,clear evidence has revealed a more complete role of ROS under both physiologic and pathologic conditions.Central to the role of ROS is the redox signaling pathways that control exercise-induced major physiologic and cellular responses and adaptations,such as mitochondrial biogenesis,mitophagy,mitochondrial morphologic dynamics,antioxidant defense,and inflammation.The current review focuses on how muscle contraction and immobilization may activate or inhibit redox signalings and their impact on muscle mitochondrial homeostasis and physiologic implications.