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Cited by 17Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchNutrition and Health in Aging

P38 Mitogen-Activated Protein Kinase Is Not Activated in the Quadriceps of Patients with Stable Chronic Obstructive Pulmonary Disease

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Riddoch-Contreras, Joanna, George, Tomasz, Natanek, Samantha A., Marsh, Gemma S., Hopkinson, Nicholas S., Tal-Singer, Ruth, Kemp, Paul, Polkey, Michael I.·2012·COPD: Journal of Chronic Obstructive Pulmonary Disease
DOI 10.3109/15412555.2011.644359
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Abstract

Quadriceps weakness is associated with a poor prognosis in COPD. Several data suggest that immobility and muscle wasting may be related through up-regulation of the p38 Mitogen associated protein kinase (MAPK) signalling pathway. We therefore hypothesised that this might occur in the quadriceps of COPD patients. We studied 105 stable COPD outpatients (mean FEV(1) 43.9% predicted) and 27 age and gender matched controls. We measured fat-free mass, quadriceps strength and daily physical activity using triaxial accelerometry. A quadriceps biopsy was obtained in which components of the p38-MAPK signalling pathway were examined. Patients had reduced fat-free mass index (16.1 (2.2) kg/m(2) vs 17.2 (2.2) kg/m(2), p = 0.02) and exhibited quadriceps weakness (mean (SD) maximal voluntary contraction force 72.1% (18.7) predicted and 82.3% (7.1) predicted for patients and controls respectively, p = 0.01). Physical activity was significantly reduced in the patient group; in particular mean (SD) locomotion time was 101 (48) minutes/12 hours in controls and 48 (31) minutes in patients (p < 0.0001). However, in biopsies obtained from these patients, no differences were observed for total or phosphorylated HSP27 or p38 MAPK protein or p38 MAPK mRNA (MAPK14); of the downstream products both GADD45β and c-jun mRNA were reduced in COPD patients while c-myc was not different from controls. No parameter correlated with physiological data within the patient group. We conclude that, despite the presence of reduced fat-free mass, quadriceps weakness and inactivity, p38 MAPK signalling was not up-regulated in skeletal muscle of stable out-patients with COPD.

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Research works printed but not linked: 52

  1. Seymour JM, Spruit MA, Hopkinson NS, et al. Th e prevalence of quadriceps weakness in COPD and the relationship with disease severity. Eur Respir J 2010; 36(1):81-88.
  2. Marquis K, Debigare R, Lacasse Y, et al. 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 2002; 166(6):809-813.
  3. Swallow EB, Reyes D, Hopkinson NS, et al. Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease. Th orax 2007; 62(2):115-120.
  4. Liu W, Liang Q, Balzar S, et al. Cell-specifi c activation profi le of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways. J Allergy Clin Immunol 2008; 121(4):893-902 e2.
  5. Renda T, Baraldo S, Pelaia G, et al. Increased activation of p38 MAPK in COPD. Eur Respir J 2008; 31(1):62-69
  6. Liu Q, Xu WG, Luo Y, et al. Cigarette smoke-induced skeletal muscle atrophy is associated with up-regulation of USP-19 via p38 and ERK MAPKs. J Cell Biochem 2011; in press.
  7. Pitta F, Troosters T, Spruit MA, et al. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171(9):972-977.
  8. Watz H, Waschki B, Meyer T, et al. Physical activity in patients with COPD. Eur Respir J 2009; 33(2):262-272.
  9. Choi I, Lee K, Kim M, et al. Diff erential activation of stress- responsive signalling proteins associated with altered loading in a rat skeletal muscle. J Cell Biochem 2005; 96(6):1231-1243.
  10. Childs TE, Spangenburg EE, Vyas DR, et al. Temporal alterations in protein signaling cascades during recovery www.copdjournal.com from muscle atrophy. Am J Physiol Cell Physiol 2003; 285(2):C391-98.
  11. Morris RT, Spangenburg EE, Booth FW. Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle. J Appl Physiol 2004; 96(1):398-404.
  12. Machida S, Booth FW. Changes in signalling molecule levels in 10-day hindlimb immobilized rat muscles. Acta Physiol Scand 2005; 183(2):171-179.
  13. Li YP, Chen Y, John J, et al. TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J 2005; 19(3):362-370.
  14. Barreiro E, Gea J, Corominas JM, et al. Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2003; 29(6):771-778.
  15. Barreiro E, Schols AM, Polkey MI, et al. Cytokine profi le in quadriceps muscles of patients with severe COPD. Th orax 2008; 63(2):100-107.
  16. Powers SK, Kavazis AN, McClung JM. Oxidative stress and disuse muscle atrophy. J Appl Physiol 2007; 102(6):2389-2397.
  17. Lemire BB, Debigaré R, Th eriault M, et al. MAPK Signaling In Th e quadriceps of patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2011; 183:A2527.
  18. Kent LM, Smyth LJ, Plumb J, et al. Inhibition of lipopolysaccharide-stimulated chronic obstructive pulmonary disease macrophage infl ammatory gene expression by dexamethasone and the p38 mitogen-activated protein kinase inhibitor N-cyano-N'-(2-{[8-(2,6-difl uorophenyl)-4-(4-fl uoro- 2-methylphenyl)-7-oxo-7 ,8-dihydropyrido[2,3-d] pyrimidin- 2-yl]amino}ethyl)guanidine (SB706504). J Pharmacol Exp Th er 2009; 328(2):458-468.
  19. Montalban AG, Boman E, Chang CD, et al. KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. Eur J Pharmacol 2010; 632(1-3):93-102.
  20. Singh D, Smyth L, Borrill Z, et al. A randomized, placebo- controlled study of the eff ects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of infl ammation in COPD patients. J Clin Pharmacol 2010; 50(1):94-100.
  21. Medicherla S, Fitzgerald MF, Spicer D, et al. p38alpha- selective mitogen-activated protein kinase inhibitor SD-282 reduces infl ammation in a subchronic model of tobacco smoke-induced airway infl ammation. J Pharmacol Exp Th er 2008; 324(3):921-929.
  22. 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(6):532-555.
  23. Steiner MC, Barton RL, Singh SJ, et al. Bedside methods versus dual energy X-ray absorptiometry for body composition measurement in COPD. Eur Respir J 2002; 19(4):626-631.
  24. Edwards RHT, Young A, Hosking GP, et al. Human skeletal muscle function: description of tests and normal values. Clin Sci 1977; 52:283-290.
  25. Polkey MI, Kyroussis D, Hamnegard C-H, et al. Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man. Muscle Nerve 1996; 19:549-555.
  26. Bergstrom L. Muscle electrolytes in man. Determination by neutron activation analysis on needle biopsy specimens. A study on normal subjects, kidney patients, and patients with chronic diarrhea. Scand J Clin Lab Invest 1962; 68:1-110.
  27. Franssen FM, Broekhuizen R, Janssen PP, et al. Limb muscle dysfunction in COPD: eff ects of muscle wasting and exercise training. Med Sci Sports Exerc 2005; 37(1):2-9.
  28. Cote CG, Casanova C, Marin JM, et al. Validation and comparison of reference equations for the 6-min walk distance test. Eur Respir J 2008; 31(3):571-578.
  29. Spruit MA, Polkey MI, Celli B, et al. Predicting Outcomes from 6-Minute Walk Distance in Chronic Obstructive Pulmonary Disease. J Amer Med Direct Asso 2011; in press.
  30. Chen S, Qiong Y, Gardner DG. A role for p38 mitogen- activated protein kinase and c-myc in endothelin-dependent rat aortic smooth muscle cell proliferation. Hypertension 2006; 47(2):252-258.
  31. Weiss C, Faust D, Durk H, et al. TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38-MAPK- dependent pathway. Oncogene 2005; 24(31):4975-4983.
  32. Marinissen MJ, Chiariello M, Gutkind JS. Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway. Genes Dev 2001; 15(5):535- 553.
  33. Sarkar D, Su ZZ, Lebedeva IV, et al. mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. Proc Natl Acad Sci USA 2002; 99(15):10054-10059.
  34. Di Giovanni S, Molon A, Broccolini A, et al. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol 2004; 55(2):195-206.
  35. Swallow EB, Barreiro E, Gosker H, et al. Quadriceps muscle strength in scoliosis. Eur Respir J 2009; 34(6):1429-1435.
  36. Wretman C, Widegren U, Lionikas A, et al. Diff erential activation of mitogen-activated protein kinase signalling pathways by isometric contractions in isolated slow-and fast-twitch rat skeletal muscle. Acta Physiol Scand 2000; 170(1):45-49.
  37. Mylabathula DB, Rice KM, Wang Z, et al. Age-associated changes in MAPK activation in fast-and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model. Exp Gerontol 2006; 41(2):205-214.
  38. Gosker H, Zeegers M, Wouters E, et al. Muscle fi bre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Th orax 2007; 62(11):944-9.
  39. Adachi T, Kikuchi N, Yasuda K, et al. Fibre type distribution and gene expression levels of both succinate dehydrogenase and peroxisome proliferator-activated receptor-gamma coactivator-1alpha of fi bres in the soleus muscle of Zucker diabetic fatty rats. Exp Physiol 2007; 92(2):449-455.
  40. Gosselink JV, Hayashi S, Elliott WM, et al. Diff erential expression of tissue repair genes in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 181(12):1329-1335.
  41. Hamnegard CH, Sedler M, Polkey MI, et al. Quadriceps strength assessed by magnetic stimulation of the femoral nerve in normal subjects. Clin Physiol Funct Imag 2004; 24(5):276-280.
  42. Csukly KJ, Martineau LC, Gardiner PF. Inter-and intra- muscle comparisons of MAPK mechanosensitivity: evidence for the absence of fi bre-type dependency. Pfl ugers Arch 2002; 444(6):732-737.
  43. Jiang F, Li P, Fornace AJ, Jr., et al. G2/M arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer. J Biol Chem 2003; 278(48):48030-48040.
  44. Buitrago CG, Ronda AC, de Boland AR, et al. MAP kinases p38 and JNK are activated by the steroid hormone 1alpha,25(OH)2- vitamin D3 in the C2C12 muscle cell line. J Cell Biochem 2006; 97(4):698-708.
  45. Janssens W, Bouillon R, Claes B, et al. Vitamin D defi ciency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Th orax 2010; 65(3):215-220.
  46. Hopkinson NS, Li KW, Kehoe A, et al. Vitamin D receptor genotypes infl uence quadriceps strength in chronic obstructive pulmonary disease. Am J Clin Nutr 2008; 87(2):385-390.
  47. Spruit MA, Gosselink R, Troosters T, et al. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Th orax 2003; 58(9):752-756.
  48. Pitta F, Troosters T, Probst VS, et al. Physical activity and hospitalization for exacerbation of COPD. Chest 2006; 129(3):536-544.
  49. Austin RL, Rune A, Bouzakri K, et al. siRNA-mediated reduction of inhibitor of nuclear factor-kappaB kinase prevents tumor necrosis factor-alpha-induced insulin resistance in human skeletal muscle. Diabetes 2008; 57(8):2066-2073.
  50. Crul T, Spruit MA, Gayan-Ramirez G, et al. Markers of infl ammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest 2007; 37(11):897-904.
  51. Seymour JM, Ward K, Sidhu P, et al. Ultrasound measurement of rectus femoris cross-sectional area and the relationship to quadriceps strength in chronic obstructive pulmonary disease. Th orax 2009; 64:418-423.
  52. Doucet M, Russell AP, Leger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007; 176(3):261-269.

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Authors
Riddoch-Contreras, J., George, T., Natanek, S. A., Marsh, G. S., Hopkinson, N. S., Tal-Singer, R., Kemp, P., & Polkey, M. I.
Affiliations
  • Imperial College London (GB)
  • Royal Brompton Hospital (GB)
Corresponding author
Polkey, Michael I.
ORCID
Venue
COPD: Journal of Chronic Obstructive Pulmonary Disease
Publisher
Informa UK Limited
Published
2012-03-12
Volume
9
Issue
2
Pages
142-150
ISSN
  • 1541-2555 (ISSN-L)
  • 1541-2563
DOI
10.3109/15412555.2011.644359
OpenAlex
W2170157172
Cited by
17
References
0
Citations by year
2023: 2 · 2018: 1 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 4
FWCI
1.42
Type
journal article
Language
en
Open access
Locations
  • COPD Journal of Chronic Obstructive Pulmonary Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust (079686)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
chronic obstructive pulmonary disease, p38 MAPK signalling, quadriceps, muscle weakness, fat-free mass, physical activity, immobility, muscle atrophy, HSP27, GADD45B, c-Jun, c-Myc, MAPK14, muscle biopsy
MeSH terms
Aged, Female, Humans, Male, Middle Aged, Motor Activity, Muscular Atrophy, Signal Transduction, Up-Regulation, Muscle Weakness, Pulmonary Disease, Chronic Obstructive, p38 Mitogen-Activated Protein Kinases, Quadriceps Muscle, Real-Time Polymerase Chain Reaction

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