TY - JOUR
T1 - Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle
AU - Petersen, Anne Marie Winther
AU - Magkos, Faidon
AU - Atherton, Philip
AU - Selby, Anna
AU - Smith, Kenneth
AU - Rennie, Michael J.
AU - Pedersen, Bente Klarlund
AU - Mittendorfer, Bettina
PY - 2007/9
Y1 - 2007/9
N2 - Smoking causes multiple organ dysfunction. The effect of smoking on skeletal muscle protein metabolism is unknown. We hypothesized that the rate of skeletal muscle protein synthesis is depressed in smokers compared with non-smokers. We studied eight smokers (≥20 cigarettes/day for ≥20 years) and eight non-smokers matched for sex (4 men and 4 women per group), age (65 ± 3 and 63 ± 3 yr, respectively; means ± SEM) and body mass index (25.9 ± 0.9 and 25.1 ± 1.2 kg/m2, respectively). Each subject underwent an intravenous infusion of stable isotope-labeled leucine in conjunction with blood and muscle tissue sampling to measure the mixed muscle protein fractional synthesis rate (FSR) and whole body leucine rate of appearance (Ra) in plasma (an index of whole body proteolysis), the expression of genes involved in the regulation of muscle mass (myostatin, a muscle growth inhibitor, and MAFBx and MuRF-1, which encode E3 ubiquitin ligases in the proteasome proteolytic pathway) and that for the inflammatory cytokine TNF-α in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-α, interleukin-6) which are associated with muscle wasting in other conditions. There were no differences between nonsmokers and smokers in plasma leucine concentration, leucine rate of appearance, and plasma concentrations of inflammatory markers, or TNF-α mRNA in muscle, but muscle protein FSR was much less (0.037 ± 0.005 vs. 0.059 ± 0.005%/h, respectively, P = 0.004), and myostatin and MAFBx (but not MuRF-1) expression were much greater (by ∼33 and 45%, respectivley, P < 0.05) in the muscle of smokers than of nonsmokers. We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia.
AB - Smoking causes multiple organ dysfunction. The effect of smoking on skeletal muscle protein metabolism is unknown. We hypothesized that the rate of skeletal muscle protein synthesis is depressed in smokers compared with non-smokers. We studied eight smokers (≥20 cigarettes/day for ≥20 years) and eight non-smokers matched for sex (4 men and 4 women per group), age (65 ± 3 and 63 ± 3 yr, respectively; means ± SEM) and body mass index (25.9 ± 0.9 and 25.1 ± 1.2 kg/m2, respectively). Each subject underwent an intravenous infusion of stable isotope-labeled leucine in conjunction with blood and muscle tissue sampling to measure the mixed muscle protein fractional synthesis rate (FSR) and whole body leucine rate of appearance (Ra) in plasma (an index of whole body proteolysis), the expression of genes involved in the regulation of muscle mass (myostatin, a muscle growth inhibitor, and MAFBx and MuRF-1, which encode E3 ubiquitin ligases in the proteasome proteolytic pathway) and that for the inflammatory cytokine TNF-α in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-α, interleukin-6) which are associated with muscle wasting in other conditions. There were no differences between nonsmokers and smokers in plasma leucine concentration, leucine rate of appearance, and plasma concentrations of inflammatory markers, or TNF-α mRNA in muscle, but muscle protein FSR was much less (0.037 ± 0.005 vs. 0.059 ± 0.005%/h, respectively, P = 0.004), and myostatin and MAFBx (but not MuRF-1) expression were much greater (by ∼33 and 45%, respectivley, P < 0.05) in the muscle of smokers than of nonsmokers. We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia.
KW - Muscle growth
KW - Protein turnover
KW - Sarcopenia
KW - Stable-isotope-labeled tracers
UR - http://www.scopus.com/inward/record.url?scp=34548452916&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00301.2007
DO - 10.1152/ajpendo.00301.2007
M3 - Article
C2 - 17609255
AN - SCOPUS:34548452916
SN - 0193-1849
VL - 293
SP - E843-E848
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 3
ER -