title: Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle.
abstract: 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 (> or =20 cigarettes/day for > or =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/m(2), 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-alpha in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-alpha, 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-alpha 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 approximately 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.
authors.affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases and Copenhagen Muscle Research Centre, Copenhagen, Denmark.
authors.forename: Anne Marie Winther
authors.initials: AM
authors.lastname: Petersen
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Philip
authors.initials: P
authors.lastname: Atherton
authors.forename: Anna
authors.initials: A
authors.lastname: Selby
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rennie
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Bettina
authors.initials: B
authors.lastname: Mittendorfer
mesh_terms: D000368:Aged; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin; D014176:Protein Biosynthesis / Q000502:physiology*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525911:MSTN protein, human; D009124:Muscle Proteins; D055435:Myostatin; D016212:Transforming Growth Factor beta; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases