An 8-week combined exercise program benefits body composition, especially lean mass, and positively affects isokinetic strength and CVD risk factors. Therefore, increasing lean mass and strength by continuously participating in a combined exercise program may be an effective treatment for preventing and improving CVD in older women.
Muscle wasting in cancer is associated with deficits in protein synthesis, yet, the mechanisms underlying this anabolic impairment remain poorly understood. The capacity for protein synthesis is mainly determined by the abundance of muscle ribosomes, which is in turn regulated by transcription of the ribosomal (r)RNA genes (rDNA). In this study, we investigated whether muscle loss in a preclinical model of ovarian cancer is associated with a reduction in ribosomal capacity and was a conse-How to cite this article: Kim H-G, Huot JR, Pin F, Guo B, Bonetto A, Nader GA. Reduced rDNA transcription diminishes skeletal muscle ribosomal capacity and protein synthesis in cancer cachexia. The
An increase in ribosomal capacity is a hallmark of the hypertrophying muscle. We review evidence demonstrating that transcription of ribosomal RNA genes is necessary for the increase in ribosomal capacity, and this is critical for muscle growth in human and animal models of hypertrophy.
Muscle wasting/cachexia is a major contributor of mortality and morbidity in cancer and is frequently accompanied by functional and metabolic muscle abnormalities. Muscle mass is determined by the balance between protein synthesis and degradation, yet very little is known about the mechanisms controlling the translational capacity (i.e., ribosome biogenesis) of skeletal muscle in cancer cachexia. Muscle ribosome content is mainly regulated by transcription of the ribosomal (r)DNA genes and also by degradation of ribosomes via ribophagy. In this study, we investigated whether muscle wasting in a previously described model for the study of ovarian cancer cachexia is associated with reduced rDNA transcription and ribosomal mass. Nod SCID gamma mice were injected with 1 × 107 ES‐2 human high‐grade serous ovarian cancer cells and observed for fourteen days. Gastrocnemius muscle was collected for qPCR and western blot analysis. Fourteen days of tumor bearing resulted in a 24% (P < 0.0001) loss in gastrocnemius muscle weight. Muscle wasting was associated with ~50% (P = 0.0003) reduction in ribosomal capacity and a significant suppression in rDNA transcription rates (35%, P = 0.0086). This was accounted by a significant reduction in specific rDNA loci. Factors associated with the regulation of rDNA transcription (i.e., Pol1rb, UBF, RRN3, TAF1C, PAF53) were significantly higher than control (1.5 to 4‐fold, P < 0.05). Muscle wasting was also associated with a 4‐fold increased expression (P < 0.0001) of the ribophagy receptor NUFIP1. Our findings indicate that in cancer cachexia, the anabolic capacity of skeletal muscle is diminished due to reduced ribosome production and likely increased ribosome degradation via ribophagy.
Support or Funding Information
Supported by NIH grant R56AR‐073385 to GAN, The Pennsylvania State University, and The Huck Institute of the Life Sciences.
This study investigated the low temperature growth of GaN on a nucleation layer in a remote plasma enhanced-ultrahigh vacuum chemical vapor deposition (RPE-UHVCVD) system which is equipped with an rf plasma cell for a nitrogen source. It was found that the growth temperature and the film thickness of the nucleation layer and the nitrogen flow rate for GaN growth play important roles in the improvement of crystallinity of the GaN layer. The nitridation of sapphire was also found to enhance the formation of facet shaped nuclei on the nucleation layer. As the temperature of the nucleation layer increased, islands with hexagonal and other facet shapes were formed on the grown GaN surface. This facet formation was related with the surface morphology and crystallinity of GaN. The best crystallinity was measured in a GaN layer with hexagonal facets on the surface and such GaN layers could be grown on a nucleation layer grown at 375 °C. Nitridation of sapphire and the growth temperature of the nucleation layer were also found to change the island shapes which enhances the formation of columnar structures in the GaN layer, resulting in the growth of a high crystalline GaN layer at low temperature.
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