Abstract
The turnover of muscle protein is responsive to different (patho)-physiological conditions but little is known about the rate of synthesis at the level of individual proteins or whether this varies between different muscles. We investigated the synthesis rate of eight proteins (actin, albumin, ATP synthase alpha, beta enolase, creatine kinase, myosin essential light chain, myosin regulatory light chain and tropomyosin) in the extensor digitorum longus, diaphragm, heart and soleus of male Wistar rats (352 ± 30 g body weight). Animals were assigned to four groups (n = 3, in each), including a control and groups that received deuterium oxide (2H2O) for 4 days, 7 days or 14 days. Deuterium labelling was initiated by an intraperitoneal injection of 10 μL/g body weight of 99.9% 2H2O-saline, and was maintained by administration of 5% (v/v) 2H2O in drinking water provided ad libitum. Homogenates of the isolated muscles were analysed by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionisation time of flight mass spectrometry. Proteins were identified against the SwissProt database using peptide mass fingerprinting. For each of the eight proteins investigated, the molar percent enrichment (MPE) of 2H and rate constant (k) of protein synthesis was calculated from the mass isotopomer distribution of peptides based on the amino acid sequence and predicted number of exchangeable C–H bonds. The average MPE (2.14% ± 0.2%) was as expected and was consistent across muscles harvested at different times (i.e., steady state enrichment was achieved). The synthesis rate of individual proteins differed markedly within each muscle and the rank-order of synthesis rates differed among the muscles studied. After 14 days the fraction of albumin synthesised (23% ± 5%) was significantly (p < 0.05) greater than for other muscle proteins. These data represent the first attempt to study the synthesis rates of individual proteins across a number of different striated muscles.
Highlights
Skeletal muscle accounts for ~40% of adult body mass and, in addition to its obvious function in movement, muscle has important roles in glucose homeostasis and protein metabolism
Because skeletal muscle is the major repository of protein/amino acids that can be mobilised during starvation or injury, muscle loss is an independent predictor of mortality in cachexia associated with diseases such as cancer and chronic heart failure [2]
Protein synthesis in vivo was investigated in the diaphragm, heart, extensor digitorum longus (EDL) and soleus of rats administered 2 H2 O for either 4 days, 7 days or 14 days
Summary
Skeletal muscle accounts for ~40% of adult body mass and, in addition to its obvious function in movement, muscle has important roles in glucose homeostasis and protein metabolism. In healthy individuals muscle is responsible for >75% of insulin-mediated glucose disposal and ~60% of total body protein turnover. Maintaining adequate muscle mass and function are important factors that impact long-term health. Age-related losses in muscle mass lead to frailty and loss of independence, and so directly impact an individual’s quality of life. Those individuals with the greatest level of muscle loss are more likely to be obese or suffer from metabolic disorders. Because skeletal muscle is the major repository of protein/amino acids that can be mobilised during starvation or injury, muscle loss is an independent predictor of mortality in cachexia associated with diseases such as cancer and chronic heart failure [2]
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