Diesel exhaust particles attenuate skeletal muscle cell proliferation and induce skeletal muscle atrophy through activation of AMP-activated protein kinase

초록

BackgroundExtensive research has been conducted on the adverse effects of particulate matter on human health, primarily focusing on its impact on the respiratory and cardiovascular systems. However, there has been limited research on the effects of particulate matter on skeletal muscle at the cellular level.ObjectiveIn this study, we investigated the effects of diesel exhaust particles on skeletal muscle at the cellular level.MethodsC2C12 myoblasts were treated with 0, 1, 3, 10, 30, or 100 mu g/mL of SRM1650b diesel exhaust particles, and viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The protein expression of key downstream molecules in the Akt signaling pathway was determined by western blotting. The relative expression of muscle-atrophy-related gene mRNA was analyzed using real-time PCR.ResultsIncubating C2C12 myotubes with diesel exhaust particles resulted in the activation of the AMP-activated protein kinase signaling pathway in a concentration- and time-dependent manner. Furthermore, the Akt/mTOR signaling pathway was inhibited in the presence of diesel exhaust particles, as evidenced by the decreased phosphorylation of Akt and downstream molecules such as mTOR, p70S6K1, and 4E-BP1. Additionally, diesel exhaust particles upregulated the expression of the muscle-atrophy-related genes MuRF-1 and MAFbx. Inhibition of AMP-activated protein kinase using compound C or AMPK alpha 2 small interfering RNA reversed the effects of diesel exhaust particles on Akt/mTOR signaling and atrophy-related gene expression.ConclusionsOur study provides valuable insights into the molecular mechanisms that underlie the harmful effects of diesel exhaust particles on skeletal muscle at the cellular level, emphasizing the significance of AMP-activated protein kinase signaling in muscle homeostasis. These findings may advance our understanding of the health risks associated with PM exposure and guide the development of preventive and therapeutic strategies.

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