CoChat
Sign Up
Cited by 133Exercise and Physiological ResponsesChronic Obstructive Pulmonary Disease (COPD) ResearchAntioxidant Activity and Oxidative Stress

Chronic Endurance Exercise Induces Quadriceps Nitrosative Stress in Patients with Severe COPD

Open access
Barreiro, E, Rabinovich, R, Marin-Corral, J, Barbera, J A, Gea, J, Roca, J·2008·Thorax
DOI 10.1136/thx.2008.105163
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Although exercise training has beneficial effects on skeletal muscle bioenergetics and exercise performance in patients with severe chronic obstructive pulmonary disease (COPD), it may also be associated with increased quadriceps oxidative and nitrosative stress. The aim of this study was to explore quadriceps oxidative and nitrosative stress in patients with severe COPD, both before and after a 3 week endurance exercise programme, and to identify the nature of the oxidatively modified proteins. METHODS: Reactive carbonyls, hydroxynonenal-protein adducts, antioxidant enzymes, nitric oxide synthase (NOS) and 3-nitrotyrosine levels were determined in the quadriceps (pre- and post-exercise) of 15 patients with severe COPD and seven healthy controls using immunoblotting (one- and two-dimensional electrophoresis), activity assays and mass spectrometry. RESULTS: At baseline, muscle levels of reactive carbonyls, which were negatively associated with muscle strength and exercise tolerance, were significantly higher in patients than in controls. Moreover, baseline hydroxynonenal-protein adducts, superoxide dismutase activity, inducible NOS and 3-nitrotyrosine immunoreactivity levels were also significantly increased in the quadriceps of patients compared with controls. In patients, chronic exercise induced a significant rise in inducible NOS levels and a fourfold increase in protein nitration. Chronic endurance exercise induced tyrosine nitration of muscle enolase 3beta, aldolase A, triosephosphate isomerase, creatine kinase, carbonic anhydrase III, myoglobin and uracil DNA glycosylase in the quadriceps of patients, while contractile protein alpha-1 actin was nitrated only in patients exhibiting muscle loss (post hoc analysis). Superoxide dismutase activity increased after the exercise programme only in controls. CONCLUSIONS: In severe COPD, chronic endurance exercise induces increased tyrosine nitration of quadriceps proteins involved in glycolysis, energy distribution, carbon dioxide hydration, muscle oxygen transfer, DNA repair and contractile function in patients exhibiting systemic effects of the disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/thx.2008.105163

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increased Mn-superoxide dismutase (SOD) and Cu-Zn-SOD protein levels have been demonstrated in COPD quadriceps, whereas unchanged SOD content and decreased SOD activity have been reported in another study, and unchanged MnSOD, Cu/ZnSOD, and catalase expressions have been found in cultured COPD myoblasts and myotubes.

    “For example, increased Mn-superoxide dismutase (SOD) and Cu-Zn-SOD protein levels have been demonstrated in the quadriceps [118,127], whereas unchanged SOD content and decreased SOD activity have been reported in another study [122], and unchanged MnSOD, Cu/ZnSOD, and catalase expressions in cultured COPD myoblasts and myotubes have been found [128].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [127]

    The Muscle redox balance section (page unavailable) reports higher baseline quadriceps SOD activity in patients with COPD than in controls. It does not report increased protein levels of Mn-SOD or Cu-Zn-SOD, which is the specific finding attributed to this paper. The other findings in the citing sentence have separate citations and are not assessed here. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In COPD, the protective mechanism of increasing antioxidants in response to oxidative stress seems defective, although contradictory data have been reported.

    “Skeletal muscle tissue usually compensates the excessive oxidative stress (induced for example by exercise training) by increasing the levels of antioxidants [122,127], but in COPD, this protective mechanism seems to be defective, although contradictory data have been reported.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [127]

    The Muscle oxidative stress section reports that exercise increased antioxidant SOD activity in healthy controls but not in patients with severe COPD, supporting a defective exercise-induced response. The Muscle redox balance section also reports higher baseline SOD activity in patients, but the paper does not identify this or other findings as contradictory reports. Its direct evidence is limited to the exercise response studied. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Several studies have found increased lipofuscin accumulation in COPD quadriceps and higher levels of 4-HNE in quadriceps tissue, as well as in cultured myotubes from COPD patients.

    “For example, several studies have found an increased lipofuscin accumulation in COPD quadriceps [126] and higher levels of hydroxy-2-nonenal (4-HNE) in quadriceps tissue [87,127], as well as in cultured myotubes from COPD patients [128].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [127]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. Thorax 2009;64:13-19. doi:10.1136/thx.2008.105163 on July 13, 2023 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thx.2008.105163 on 3 October 2008. Downloaded from REFERENCES
  2. Casaburi R, Patessio A, Ioli F, et al. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 1991;143:9-18.
  3. Gosselink R, Troosters T, Decramer M. Exercise training in COPD patients: the basic questions. Eur Respir J 1997;10:2884-91.
  4. Maltais F, LeBlanc P, Simard C, et al. Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;154:442-7.
  5. Sala E, Roca J, Marrades RM, et al. Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1726-34.
  6. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007;176: 532-55.
  7. Casaburi R, Porszasz J, Burns MR, et al. Physiologic benefits of exercise training in rehabilitation of patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:1541-51.
  8. Maltais F, LeBlanc P, Jobin J, et al. Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:555-61.
  9. Barreiro E, Gea J, Corominas JM, et al. Nitric oxide synthases and protein oxidation in the quadriceps femoris of COPD patients. Am J Respir Cell Mol Biol 2003;29:771-8.
  10. Barreiro E, Gea J, Matar G, et al. Expression and carbonylation of creatine kinase in the quadriceps femoris muscles of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2005;33:636-42.
  11. Barreiro E, de la Puente B, Minguella J, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:1116-24.
  12. Heunks LM, Vina J, van Herwaarden CL, et al. Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol 1999;277:R1697-704.
  13. Koechlin C, Couillard A, Simar D, et al. Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2004;169:1022-7.
  14. Rabinovich RA, Ardite E, Troosters T, et al. Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:1114-18.
  15. Barreiro E, Galdiz JB, Marinan M, et al. Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects. J Appl Physiol 2006;100:555-63.
  16. Rabinovich RA, Ardite E, Mayer AM, et al. Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index. Respiration 2006;73:757-61.
  17. Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med 2004;351:2112-14.
  18. Richardson RS, Leek BT, Gavin TP, et al. Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO 2 with small muscle mass exercise. Am J Respir Crit Care Med 2004;169:89-96.
  19. Schols AM, Buurman WA, Staal van den Brekel AJ, et al. Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 1996;51:819-24.
  20. Barreiro E, Schols AM, Polkey MI, et al. Cytokine profile in quadriceps muscles of patients with severe COPD. Thorax 2008;63:100-7.
  21. Rabinovich RA, Bastos R, Ardite E, et al. Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J 2007;29:643-50.
  22. Barreiro E, Gea J, Di Falco M, et al. Protein carbonyl formation in the diaphragm. Am J Respir Cell Mol Biol 2005;32:9-17.
  23. Coin A, Sergi G, Minicuci N, et al. Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80-year-old Italian population. Clin Nutr 2008;27:87-94.
  24. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med 1996;153:976-80.
  25. Bernard S, LeBlanc P, Whittom F, et al. Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158:629-34.
  26. Barreiro E, Comtois AS, Gea J, et al. Protein tyrosine nitration in the ventilatory muscles: role of nitric oxide synthases. Am J Respir Cell Mol Biol 2002;26:438-46.
  27. Montes de Oca M, Torres SH, De Sanctis J, et al. Skeletal muscle inflammation and nitric oxide in patients with COPD. Eur Respir J 2005;26:390-7.
  28. Agustı ´A, Morla ´M, Sauleda J, et al. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax 2004;59:483-7.
  29. Vassilakopoulos T, Deckman G, Kebbewar M, et al. Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training. Am J Physiol Lung Cell Mol Physiol 2003;284:L452-7.
  30. Castegna A, Thongboonkerd V, Klein JB, et al. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J Neurochem 2003;85:1394-401.
  31. Peluffo G, Radi R. Biochemistry of protein tyrosine nitration in cardiovascular pathology. Cardiovasc Res 2007;75:291-302.
  32. Gole MD, Souza JM, Choi I, et al. Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 2000;278:L961-7.
  33. MacMillan-Crow LA, Crow JP, Kerby JD, et al. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci U S A 1996;93:11853-8.
  34. Souza JM, Choi I, Chen Q, et al. Proteolytic degradation of tyrosine nitrated proteins. Arch Biochem Biophys 2000;380:360-6.
  35. Hussain SN, Matar G, Barreiro E, et al. Modifications of proteins by 4-hydroxy-2- nonenal in the ventilatory muscles of rats. Am J Physiol Lung Cell Mol Physiol 2006;290:L996-1003.
  36. Fugere NA, Ferrington DA, Thompson LV. Protein nitration with aging in the rat semimembranosus and soleus muscles. J Gerontol A Biol Sci Med Sci 2006;61:806-12.
  37. Koeck T, Levison B, Hazen SL, et al. Tyrosine nitration impairs mammalian aldolase A activity. Mol Cell Proteomics 2004;3:548-57.
  38. Mihm MJ, Coyle CM, Schanbacher BL, et al. Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure. Cardiovasc Res 2001;49:798-807.
  39. Nicolis S, Pennati A, Perani E, et al. Easy oxidation and nitration of human myoglobin by nitrite and hydrogen peroxide. Chemistry 2006;12:749-57.
  40. Snook JH, Li J, Helmke BP, et al. Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of motility. Free Radic Biol Med 2008;44:14-23.
  41. Dong M, Vongchampa V, Gingipalli L, et al. Development of enzymatic probes of oxidative and nitrosative DNA damage caused by reactive nitrogen species. Mutat Res 2006;594:120-34.
  42. Schols AM, Broekhuizen R, Weling-Scheepers CA, et al. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 2005;82:53-9.
  43. Vestbo J, Prescott E, Almdal T, et al. Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City Heart Study. Am J Respir Crit Care Med 2006;173:79-83.

Cited by

Sorted by citations

Authors
Barreiro, E., Rabinovich, R., Marin-Corral, J., Barbera, J. A., Gea, J., & Roca, J.
Affiliations
  • Municipal Institute for Medical Research (ES)
  • Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
  • Universitat Autònoma de Barcelona (ES)
Corresponding author
Barreiro, E
ORCID
Venue
Thorax
Publisher
BMJ
Published
2008-10-03
Volume
64
Issue
1
Pages
13-19
ISSN
0040-6376 (ISSN-L)
DOI
10.1136/thx.2008.105163
OpenAlex
W2123848794
Cited by
133
References
3
Citations by year
2026: 3 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 12 · 2012: 14
FWCI
12.48
Type
journal article
Language
en
Open access
Locations
  • Thorax (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Instituto de Salud Carlos III
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
chronic obstructive pulmonary disease, endurance training, nitrosative stress, oxidative stress, quadriceps, tyrosine nitration, nitrotyrosine, inducible nitric oxide synthase, superoxide dismutase, muscle mass loss, exercise tolerance, skeletal muscle
MeSH terms
Humans, Male, Middle Aged, Tyrosine, Exercise, Nitrosation, Case-Control Studies, Oxidative Stress, Pulmonary Disease, Chronic Obstructive, Quadriceps Muscle, Nitric Oxide Synthase Type II

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review