Oxidative Stress and Respiratory Muscle Dysfunction

  • Kazuto MatsunagaEmail author
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


The respiratory muscle dysfunction due to muscle atrophy can occur in numerous pathologies such as cancer, collagen disease, chronic obstructive pulmonary disease (COPD), and diaphragm unloading via mechanical ventilation. Several proteolytic pathways including lysosomal proteases such as calpain and ubiquitin proteasome systems are involved in the degradation of muscle proteins, and abundant evidence implicates oxidative stress as a potential regulator of proteolytic pathways leading to muscle atrophy. Several lines of evidence demonstrate that an increase in protein oxidation is involved in the increased diaphragmatic proteolysis during mechanical ventilation. Also, skeletal muscle dysfunction is associated with poor health status in patients with COPD. Recent evidence supports a strong role for oxidative/nitrative stress in depressed skeletal muscle strength and endurance in COPD. A growing number of studies suggest that antioxidant can serve as therapeutic agents in delaying the muscle atrophy. This chapter will address the role of oxidative and nitrative stress in muscle dysfunction of respiratory diseases.


Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Patient Muscle Atrophy Severe Chronic Obstructive Pulmonary Disease Control Mechanical Ventilation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Activator protein-1


Amyotrophic lateral sclerosis


Chronic obstructive pulmonary disease


Controlled mechanical ventilation


Forced expiratory volume in 1 second


Heat shock protein

MAP kinase

Mitogen-activated protein kinase


Matrix metalloproteases


Nuclear factor κ-B pathways


Reactive nitrogen species


Reactive oxygen species


Superoxide dismutase


Conflict of Interest Statement

No potential conflicts of interest existed with any company or organization whose products or services may have been discussed in this chapter.


  1. 1.
    Mead J (1979) Functional significance of the area of apposition of diaphragm to rib cage. Am Rev Respir Dis 119:31–32PubMedGoogle Scholar
  2. 2.
    De Troyer A, Kelly S, Zin WA (1983) Mechanical action of the intercostal muscles act on the ribs. Science 220:87–88PubMedCrossRefGoogle Scholar
  3. 3.
    De Troyer A, Sampson M, Sigrist S et al (1983) How the abdominal muscles act on the rib cage. J Appl Physiol 54:465–469PubMedGoogle Scholar
  4. 4.
    Legrand A, Schneider E, Gevenois P et al (2003) Respiratory effects of the scalene and sternomastoid muscles in humans. J Appl Physiol 94:1467–1472PubMedGoogle Scholar
  5. 5.
    Chia LG (1991) Locked-in syndrome with bilateral ventral midbrain infarcts. Neurology 41:445–446PubMedCrossRefGoogle Scholar
  6. 6.
    Hasselgren PO, Fischer JE (1997) The ubiquitin-proteasome pathway: review of a novel intracellular mechanism of muscle protein breakdown during sepsis and other catabolic conditions. Ann Surg 225:307–316PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Jagoe RT, Goldberg AL (2001) What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care 4:183–190PubMedCrossRefGoogle Scholar
  8. 8.
    Booth FW (1982) Effect of limb immobilization on skeletal muscle. J Appl Physiol 52: 1113–1118PubMedGoogle Scholar
  9. 9.
    Barnes PJ, Celli BR (2009) Systemic manifestations and comorbidities of COPD. Eur Respir J 33:1165–1185PubMedCrossRefGoogle Scholar
  10. 10.
    Gosker HR, Kubat B, Schaart G et al (2003) Myopathological features in skeletal muscle strength in chronic obstructive pulmonary disease. Eur Respir J 22:280–285PubMedCrossRefGoogle Scholar
  11. 11.
    Montes de Oca M, Torres SH, Gonzalez Y et al (2006) Peripheral muscle composition and health status in patients with COPD. Respir Med 100:1800–1806PubMedCrossRefGoogle Scholar
  12. 12.
    Powers SK, Kavazis AN, DeRuisseau KC (2005) Mechanisms of disuse muscle atrophy: role of oxidative stress. Am J Physiol Regul Integr Comp Physiol 288:337–344CrossRefGoogle Scholar
  13. 13.
    Booth FW, Seider MJ (1979) Early change in skeletal muscle protein synthesis after limb immobilization of rats. J Appl Physiol 47:974–977PubMedGoogle Scholar
  14. 14.
    Thomason DB, Biggs RB, Booth FW (1989) Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle. Am J Physiol Regul Integr Comp Physiol 257: 300–305Google Scholar
  15. 15.
    Gayan-Ramirez G, de Paepe K, Cadot P et al (2003) Detrimental effects of short-term mechanical ventilation on diaphragm function and IGF-1 mRNA in rats. Intensive Care Med 29:825–833PubMedGoogle Scholar
  16. 16.
    Le Bourdelles G, Viires N, Boczkowski J et al (1994) Effects of mechanical ventilation on diaphragmatic contractile properties in rats. Am J Respir Crit Care Med 149:1539–1544PubMedCrossRefGoogle Scholar
  17. 17.
    Shanely RA, Zergeroglu MA, Lennon SL et al (2002) Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. Am J Respir Crit Care Med 166:1369–1374PubMedCrossRefGoogle Scholar
  18. 18.
    Schanely RA, Van Gammeren D, DeRuisseau KC et al (2004) Mechanical ventilation depreses protein synthesis in the rat diaphragm. Am J Respir Crit Care Med 170:994–999CrossRefGoogle Scholar
  19. 19.
    Furuno K, Goldberg AL (1986) The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism. Biochem J 237:859–864PubMedCentralPubMedGoogle Scholar
  20. 20.
    Purintrapiban J, Wang M, Forsberg NE (2003) Degradation of sarcomeric and cytoskeletal proteins in cultured skeletal muscle cells. Comp Biochem Physiol B Biochem Mol Biol 136: 393–401PubMedCrossRefGoogle Scholar
  21. 21.
    Du J, Wang X, Miereles C et al (2004) Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 113:115–123PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Tidball JG, Spencer MJ (2002) Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse. J Physiol 545:819–828PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Goll DE, Thompson VF, Li H et al (2003) The calpain system. Physiol Rev 83:731–801PubMedGoogle Scholar
  24. 24.
    Wray CJ, Sun X, Gang GI et al (2002) Dantrolene down-regulates the gene expression and activity of the ubiquitin-proteasome proteolytic pathway in septic skeletal muscle. J Surg Res 104:82–87PubMedCrossRefGoogle Scholar
  25. 25.
    Koh TJ, Tidball JG (2000) Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells. Am J Physiol Cell Physiol 279:806–812Google Scholar
  26. 26.
    Kondo H, Nishino K, Itokawa Y (1994) Hydroxyl radical generation in skeletal muscle atropined by immobilization. FEBS Lett 349:169–172PubMedCrossRefGoogle Scholar
  27. 27.
    Siems W, Capuozzo E, Lucano A et al (2002) High sensitivity of plasma membrane ion transport ATPases from human neutrophils towards 4-hydroxy-2,3-trans-nonenal. Life Sci 166: 1369–1374Google Scholar
  28. 28.
    Primeau AJ, Adhihetty PJ, Hood DA (2002) Apoptosis in heart and skeletal muscle. Can J Appl Physiol 27:349–395PubMedCrossRefGoogle Scholar
  29. 29.
    Levine S, Nguyen T, Taylor N et al (2008) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358:1327–1335PubMedCrossRefGoogle Scholar
  30. 30.
    Chen M, Won DJ, Krajewski S et al (2002) Calpain and mitochondria in ischemia/reperfusion injury. J Biol Chem 277:29181–29186PubMedCrossRefGoogle Scholar
  31. 31.
    Leeuwenburgh C (2003) Role of apoptosis in sarcopenia. J Gerontol A Biol Sci Med Sci 58:999–1001PubMedCrossRefGoogle Scholar
  32. 32.
    Grune T, Davies KJ (2003) The proteasomal system and HNE-modified proteins. Mol Aspects Med 24:195–204PubMedCrossRefGoogle Scholar
  33. 33.
    Grune T, Merker K, Sandig G et al (2003) Selective degradation of oxidatively modified protein substances by the proteasome. Biochem Biophys Res Commun 305:709–718PubMedCrossRefGoogle Scholar
  34. 34.
    Hasselgren PO, Wray C, Mammen J (2002) Molecular regulation of muscle cahexia: it may be more than the proteasome. Biochem Biophys Res Commun 290:1–10PubMedCrossRefGoogle Scholar
  35. 35.
    DeMaritno GN, Ordway GA (1998) Ubiquitin-proteasome pathway of intracellular protein degradation: implications for muscle atrophy during unloading. Exerc Sport Sci Rev 26: 219–252Google Scholar
  36. 36.
    Li YP, Chen Y, Li AS et al (2003) Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol 285:806–812CrossRefGoogle Scholar
  37. 37.
    Bodine SC, Latres E, Baumhueter S et al (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708PubMedCrossRefGoogle Scholar
  38. 38.
    Gomes MD, Lecker SH, Jagoe RT et al (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98:14440–14445PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Reid MB (2001) Redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol 90:724–731PubMedCrossRefGoogle Scholar
  40. 40.
    Kondo H (2000) Oxidative stress in skeletal muscle atrophy. In: Chandan Sen LP, Hanninen O (eds) Handbook of oxidants and antioxidants in exercise. Elsevier, Amsterdam, pp 631–653Google Scholar
  41. 41.
    Kondo H, Miura M, Itokawa Y (1993) Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. Pflugers Arch 422:404–406PubMedCrossRefGoogle Scholar
  42. 42.
    Lawler JM, Song W, Demaree SR (2003) Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. Free Radic Biol Med 35:9–16PubMedCrossRefGoogle Scholar
  43. 43.
    Zergeroglu MA, McKenzie MJ, Shanely RA et al (2003) Mechanical ventilation-induced oxidative stress in the diaphragm. J Appl Physiol 95:1116–1124PubMedGoogle Scholar
  44. 44.
    Hellsten Y (2000) The role of xanthine oxidase in exercise. In: Chandan Sen LP, Hanninen O (eds) Handbook of oxidants and antioxidants in exercise. Elsevier, Amsterdam, pp 53–176Google Scholar
  45. 45.
    Halliwell B, Gutterridge J (1999) Free radicals in biology and medicine. Oxford University Press, LondonGoogle Scholar
  46. 46.
    Kaminski HJ, Andrade FH (2001) Nitric oxide: biologic effects on muscle and role in muscle disease. Neuromuscul Disord 11:517–524PubMedCrossRefGoogle Scholar
  47. 47.
    Kondo H, Miura M, Kodama J et al (1992) Role of iron in oxidative stress in skeletal muscle atophied by immobilization. Pflugers Arch 421:295–297PubMedCrossRefGoogle Scholar
  48. 48.
    Kondo H, Miura M, Nakagaki I et al (1992) Trace element movement and oxidative stress in seletal muscle atrophied by immobilization. Am J Physiol Endocrinol Metab 262:583–590Google Scholar
  49. 49.
    Javesghani D, Magder SA, Barreiro E et al (2002) Molecular characterization of a superoxide-generating NAD(P)H oxidase in the ventilatory muscles. Am J Respir Crit Care Med 165: 12–418CrossRefGoogle Scholar
  50. 50.
    Jackson MJ (2000) Exercise and oxygen radical production by muscle. In: Chandan Sen LP, Hanninen O (eds) Handbook of oxidants and antioxidants in exercise. Elsevier, Amsterdam, pp 57–68Google Scholar
  51. 51.
    Powers SK, Jackson MJ (2007) Exercise-induced oxidative stress: mechanisms and impact on muscle force production. Physiol Rev 88:1243–1276CrossRefGoogle Scholar
  52. 52.
    Allen RG, Tresini M (2000) Oxidative stress and gene regulation. Free Radic Biol Med 28:463–499PubMedCrossRefGoogle Scholar
  53. 53.
    Ji LL (2007) Antioxidant signaling in skeletal muscle: a brief review. Exp Gerontol 42:582–593PubMedCrossRefGoogle Scholar
  54. 54.
    McArdle A, Patwell D, Vasilaki A et al (2001) Contractile activity induced oxidative stress: cellular origin and adaptive responses. Am J Physiol Cell Physiol 280:621–627Google Scholar
  55. 55.
    Khassaf M, Child RB, McArdle A et al (2001) Time course of responses of human skeletal musvle to oxidative stress induced by nondamaging exercise. J Appl Physiol 90:1031–1035PubMedGoogle Scholar
  56. 56.
    Khassaf M, McArdle A, Esanu C et al (2003) Effect of vitamin C supplements on antioxidant defence and stress proteins in human lymphocytes and skeletal muscle. J Physiol 549: 645–652PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Jackson MJ, Khassaf M, Vasilaki A et al (2004) Vitamin E and the oxidative stress of exercise. Ann N Y Acad Sci 1031:158–168PubMedCrossRefGoogle Scholar
  58. 58.
    Zhou LZ, Johnson AP, Rando TA (2001) NFκB and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells. Free Radic Biol Med 31:1405–1416PubMedCrossRefGoogle Scholar
  59. 59.
    Jackson MJ, Papa S, Bolanos J et al (2002) Antioxidants, reactive oxygen, and nitrogen species, gene induction and mitochondrial function. Mol Aspects Med 23:209–285PubMedCrossRefGoogle Scholar
  60. 60.
    Appel HJ, Duarte JA, Soares JM (1997) Supplementation of vitamin E may attenuates skeletal muscle immobilization atrophy. Int J Sports Med 18:157–160CrossRefGoogle Scholar
  61. 61.
    Ikemoto M, Nikawa T, Kano M et al (2002) Cysteine supplementation prevents unweightind-induced ubiquitination in association with redox regulation in rat skeletal muscle. Biol Chem 383:715–721PubMedGoogle Scholar
  62. 62.
    Koesterer TJ, Dodd SL, Powers S (2002) Increased antioxidant capacity does not attenuate muscle atrophy caused by unweighting. J Appl Physiol 93:1959–1965PubMedGoogle Scholar
  63. 63.
    Jubran A, Tobin M (1997) Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med 155: 906–915PubMedCrossRefGoogle Scholar
  64. 64.
    Vassilakopoulos T, Zakynthions S, Roussos C (1998) The tension-time index and the frequency/tidal volume ration are the major pathophysiologic determinants of weaning failure and success. Am J Respir Crit Care Med 158:378–385PubMedCrossRefGoogle Scholar
  65. 65.
    Jaber S, Petrof BJ, Jung B et al (2011) Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med 183:364–371PubMedCrossRefGoogle Scholar
  66. 66.
    Gosselink R, Troosters T, Decramer M (1996) Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med 153:976–980PubMedCrossRefGoogle Scholar
  67. 67.
    Simpson K, Killian K, McCartney N et al (1992) Randomised controlled trial of weightlifting exercise in patients with chronic airflow limitation. Thorax 47:70–75PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Decramer M, Gosselink R, Troosters T et al (1997) Muscle weakness is related to utilization of health care resources in COPD patients. Eur Respir J 10:417–423PubMedCrossRefGoogle Scholar
  69. 69.
    Swallow EB, Reyes D, Hopkinson NS et al (2007) Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease. Thorax 62:115–120PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Rabe KF, Hurd S, Anzueto A et al (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176:532–555PubMedCrossRefGoogle Scholar
  71. 71.
    Man WD, Kemp P, Moxham J et al (2009) Exercise and muscle dysfunction in COPD: implications for pulmonary rehabilitation. Clin Sci (Lond) 117:281–291CrossRefGoogle Scholar
  72. 72.
    Man WD, Mustfa N, Nikoletou D et al (2004) Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD. Thorax 59:471–476PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Gray-Donald K, Gibbons L, Shapiro SH et al (1996) Nutritional status and mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 153:961–966PubMedCrossRefGoogle Scholar
  74. 74.
    Bernard S, LeBlanc P, Whittom F et al (1998) Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158:629–634PubMedCrossRefGoogle Scholar
  75. 75.
    Man WD, Soliman MG, Nikoletou D et al (2003) Non-volitional assessment of skeletal muscle strength in patients with chronic obstructive pulmonary disease. Thorax 58:665–669PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Man WD, Hopkinson NS, Harraf F et al (2005) Abdominal muscle and quadriceps strength in chronic obstructive pulmonary disease. Thorax 60:718–722PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Franssen FM, Broekhuizen R, Janssen PP et al (2005) Limb muscle dysfunction in COPD: effects of muscle wasting and exercise training. Med Sci Sports Exerc 37:2–9PubMedCrossRefGoogle Scholar
  78. 78.
    Allaire J, Maltais F, Doyon JF et al (2004) Peripheral muscle endurance and the oxidative profile of the quadriceps in patients with COPD. Thorax 59:673–678PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Man WD, Soliman MG, Gearing J et al (2003) Symptoms and quadriceps fatigability after walking and cycling in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 168:562–567PubMedCrossRefGoogle Scholar
  80. 80.
    Mador MJ, Deniz O, Aggarwal A et al (2003) Quadriceps fatigability after single muscle exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 168:102–108PubMedCrossRefGoogle Scholar
  81. 81.
    Coronell C, Orozco-Levi M, Mendez R et al (2004) Relevance of assessing quadriceps endurance in patients with COPD. Eur Respir J 24:129–136PubMedCrossRefGoogle Scholar
  82. 82.
    Pitta F, Troosters T, Probst VS et al (2008) Are patients with COPD more active after pulmonary rehabilitation? Chest 134:273–280PubMedCrossRefGoogle Scholar
  83. 83.
    Fujino F, Minakata Y, Koarai A et al (2009) The regulated factors of exercise tolerance and improvement in exercise tolerance in COPD patients. Kokyu (in Japanese) 28:653–661Google Scholar
  84. 84.
    Honda Y, Minakata Y, Sugino A et al (2012) The effect of short-acting beta 2 agonist on the exercise capacity of patients with COPD. Kokyu (in Japanese) 31:1058–1064Google Scholar
  85. 85.
    Bellemare F, Grassino A (1983) Force reserve of the diaphragm in patients with chronic obstructive pulmonary disease. J Appl Physiol 55:8–15PubMedGoogle Scholar
  86. 86.
    Polkey MI, Kyroussis D, Hamnegard CH et al (1996) Diaphragm strength in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 154:1310–1317PubMedCrossRefGoogle Scholar
  87. 87.
    Gosselink R, Troosters T, Decramer M (2000) Distribution of muscle weakness in patients with stable chronic obstructive pulmonary disease. J Cardiopulm Rehabil 20:353–360PubMedCrossRefGoogle Scholar
  88. 88.
    Serres I, Gautier V, Varray A et al (1998) Impaired skeletal muscle endurance related to physical inactivity and altered lung function in COPD patients. Chest 113:900–905PubMedCrossRefGoogle Scholar
  89. 89.
    Van’t Hul A, Harlaar J, Gosselink R et al (2004) Quadriceps muscle endurance in patients with chronic obstructive pulmonary disease. Muscle Nerve 29:267–274CrossRefGoogle Scholar
  90. 90.
    Swallow EB, Gosker HR, Ward KA et al (2007) A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans. J Appl Physiol 103:739–746PubMedCrossRefGoogle Scholar
  91. 91.
    Engelen MP, Schols AM, Does JD et al (2000) Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 71:733–738PubMedGoogle Scholar
  92. 92.
    Marquis K, Debigare R, Lacasse Y et al (2002) Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166:809–813PubMedCrossRefGoogle Scholar
  93. 93.
    Hopkinson NS, Tennant RC, Dayer MJ et al (2007) A prospective study of decline in fat free mass and skeletal muscle strength in chronic obstructive pulmonary disease. Respir Res 8:25PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Mathur S, Takai KP, Macintyre DL et al (2008) Estimation of thigh muscle mass with magnetic resonance imaging in older adults and people with chronic obstructive pulmonary disease. Phys Ther 88:219–230PubMedCrossRefGoogle Scholar
  95. 95.
    Seymour JM, Ward K, Sidhu PS et al (2009) Ultrasound measurement of rectus femoris cross-sectional area and the relationship with quadriceps strength in COPD. Thorax 64:418–423PubMedCrossRefGoogle Scholar
  96. 96.
    Engelen MP, Schols AM, Does JD et al (2000) Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema. Am J Respir Crit Care Med 161:98–103PubMedCrossRefGoogle Scholar
  97. 97.
    Debigare R, Cote CH, Hould FS et al (2003) In vitro and in vivo contractile properties of the vastus lateralis muscle in males with COPD. Eur Respir J 21:273–278PubMedCrossRefGoogle Scholar
  98. 98.
    Malaguti C, Nery LE, Dal Corso S et al (2006) Scaling skeletal muscle function to mass in patients with moderate-to-severe COPD. Eur J Appl Physiol 98:482–488PubMedCrossRefGoogle Scholar
  99. 99.
    Mador MJ, Kufel TJ, Pineda L (2000) Quadriceps fatigue after cycle exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161:447–453CrossRefGoogle Scholar
  100. 100.
    Ottenheijm CA, Heunks LM, Sieck GC et al (2005) Diaphragm dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 172:200–205PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Stubbings AK, Moore AJ, Dusmet M et al (2008) Physiological properties of human diaphragm muscle fibers and the effect of chronic obstructive pulmonary disease. J Physiol 586:2637–2650PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Whittom F, Jobin J, Simard PM et al (1998) Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc 30:1467–1474PubMedCrossRefGoogle Scholar
  103. 103.
    Maltais F, Sullivan MJ, LeBlanc P et al (1999) Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD. Eur Respir J 13:850–854PubMedCrossRefGoogle Scholar
  104. 104.
    Gosker HR, Zeegers MP, Wouters EF et al (2007) Muscle fiber type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 62:944–949PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Levine S, Kaiser L, Leferovich J et al (1997) Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. N Engl J Med 337:1799–1806PubMedCrossRefGoogle Scholar
  106. 106.
    Mercadier JJ, Schwartz K, Schiaffino S et al (1998) Myosin heavy chain gene expression changes in the diaphragm of patients with chronic lung hyperinflation. Am J Physiol 274:527–534Google Scholar
  107. 107.
    Levine S, Nguyen T, Friscia M et al (2006) Parasternal intercostal muscle remodeling in severe chronic obstructive pulmonary disease. J Appl Physiol 101:1297–1302PubMedCrossRefGoogle Scholar
  108. 108.
    Jobin J, Maltais F, Doyon JF et al (1998) Chronic obstructive pulmonary disease: capillarity and fiber-type characteristics of skeletal muscle. J Cardiopulm Rehabil 18:432–437PubMedCrossRefGoogle Scholar
  109. 109.
    Richardson RS, Leek BT, Gavin TP et al (2004) Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO2 with small muscle mass exercise. Am J Respir Crit Care Med 169:89–96PubMedCrossRefGoogle Scholar
  110. 110.
    Ichinose M, Sugiura H, Yamagata S et al (2000) Increase in reactive nitrogen species production in chronic obstructive pulmonary disease airways. Am J Respir Crit Care Med 162: 701–706PubMedCrossRefGoogle Scholar
  111. 111.
    Whiteman M, Halliwell B (1997) Prevention of peroxynitrite-dependent tyrosine nitration and inactivation of alpha1-antiproteinase by antibiotics. Free Radic Res 26:49–56PubMedCrossRefGoogle Scholar
  112. 112.
    Okamoto T, Akaike T, Sawa T et al (2001) Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem 276:29596–29602PubMedCrossRefGoogle Scholar
  113. 113.
    Zhu YK, Liu XD, Skold MC et al (2001) Cytokine inhibition of fibroblast-induced gel contraction is mediated by PGE(2) and NO acting through separate parallel pathways. Am J Respir Cell Mol Biol 25:245–253PubMedCrossRefGoogle Scholar
  114. 114.
    Ichikawa T, Sugiura H, Koarai A et al (2008) Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol 295:800–808CrossRefGoogle Scholar
  115. 115.
    Osoata GO, Hanazawa T, Brindicci C et al (2009) Peroxynitrite elevation in exhaled breath condensate of COPD and its inhibition by fudosteine. Chest 135:1513–1520PubMedCrossRefGoogle Scholar
  116. 116.
    Sugiura H, Ichinose M, Yamagata S et al (2003) Correlation between change in pulmonary function and suppression of reactive nitrogen species production following steroid treatment in COPD. Thorax 58:299–305PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Hirano T, Yamagata T, Gohda M et al (2006) Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline. Thorax 61: 761–766PubMedCentralPubMedCrossRefGoogle Scholar
  118. 118.
    Couillard A, Maltais F, Saey D et al (2003) Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 167:1664–1669PubMedCrossRefGoogle Scholar
  119. 119.
    Allaire J, Maltais F, LeBlanc P et al (2002) Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Muscle Nerve 25:383–389PubMedCrossRefGoogle Scholar
  120. 120.
    Couillard A, Koechlin C, Cristol JP et al (2002) Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients. Eur Respir J 20: 1123–1129PubMedCrossRefGoogle Scholar
  121. 121.
    van Helvoort HA, Heijdra YF, Heunks LM et al (2006) Supplemental oxygen prevents exercise-induced oxidative stress in muscle-wasted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 173:1122–1129PubMedCrossRefGoogle Scholar
  122. 122.
    Barreiro E, Rabinovich R, Marin-Corral J et al (2009) Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD. Thorax 64:13–19PubMedCrossRefGoogle Scholar
  123. 123.
    Koechlin C, Couillard A, Simar D et al (2004) Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 169:1022–1027PubMedCrossRefGoogle Scholar
  124. 124.
    Mitch WE, Goldberg AL (1996) Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 335:1897–1905PubMedCrossRefGoogle Scholar
  125. 125.
    Buck M, Chojkier M (1996) Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 15:1753–1765PubMedCentralPubMedGoogle Scholar
  126. 126.
    Stadtman ER (1990) Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med 9:315–325PubMedCrossRefGoogle Scholar
  127. 127.
    Barreiro E, Gea J, Corominas JM et al (2003) Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 29:771–778PubMedCrossRefGoogle Scholar
  128. 128.
    Montes de Oca M, Torres SH, De Sanctis J et al (2005) Skeletal muscle inflammation and nitric oxide in patients with COPD. Eur Respir J 26:390–397PubMedCrossRefGoogle Scholar
  129. 129.
    Barreiro E, de la Puente B, Minguella J et al (2005) Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 171:1116–1124PubMedCrossRefGoogle Scholar
  130. 130.
    Wijnhoven HJ, Heunks LM, Geraedts MC et al (2006) Oxidative and nitrosative stress in the diaphragm of patients with COPD. Int J Chron Obstruct Pulmon Dis 1:173–179PubMedCentralPubMedGoogle Scholar
  131. 131.
    Gosker HR, Schrauwen P, Hesselink MK et al (2003) Uncoupling protein-3 content is decreased in peripheral skeletal muscle of patients with COPD. Eur Respir J 22:88–93PubMedCrossRefGoogle Scholar
  132. 132.
    Rabinovich RA, Bastos R, Ardite E et al (2007) Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J 29:643–650PubMedCrossRefGoogle Scholar
  133. 133.
    Russell AP, Somm E, Debigare R et al (2004) COPD results in a reduction in UCP3 long mRNA and UCP3 protein content in types I and IIa skeletal muscle fibers. J Cardiopulm Rehabil 24:332–339PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Third Department of Internal Medicine, School of MedicineWakayama Medical UniversityWakayamaJapan

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