Journal Information
Vol. 43. Issue 1.
Pages 4-8 (January 2007)
Share
Share
Download PDF
More article options
Vol. 43. Issue 1.
Pages 4-8 (January 2007)
Original Articles
Full text access
Reduced Expression of the Sarcoplasmic Calcium Pump SERCA2 in Skeletal Muscle From Patients With Chronic Obstructive Pulmonary Disease and Low Body Weight
Visits
3462
Montse Morlàa, Amanda Iglesiasa, Jaume Sauledab, Borja Cosiob, Àlvar Agustía,b, Xavier Busquetsa,c,
Corresponding author
busquets@hsd.es

Correspondence: Dr. X. Busquets. Unidad de Investigación. Hospital Universitario Son Dureta (Edificio D, primera planta). Andrea Doria, 55. 07014 Palma de Mallorca. Baleares. España
a Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Baleares, Spain
b Servei de Pneumologia, Hospital Universitari Son Dureta, Palma de Mallorca, Baleares, Spain
c Departament de Biologia, Universitat Illes Balears (UIB), Palma de Mallorca, Baleares, Spain
This item has received
Article information
Abstract
Bibliography
Download PDF
Statistics
Objective

To compare the concentrations and extent of nitration of sarcoplasmic-endoplasmic reticulum Ca2+ adenosine triphosphatase 2 (SERCA2) in biopsies of the quadriceps femoris from patients with chronic obstructive pulmonary disease (COPD) who have normal or low body mass index (BMI).

Patients and methods

The patients were divided into 2 groups (n=7, each group), one containing individuals with normal BMI (>21 kg/m2) and the other with low BMI (<21 kg/m2). Forced spirometry and blood gas analysis were performed in both groups and percutaneous needle biopsies of the lateral portion of the quadriceps femoris muscle were performed. Western blots were used to assess the concentration of SERCA2 in the biopsy material. To determine whether or not the protein was tyrosine-nitrated, immunoprecipitation of SERCA2 was performed with an antinitrotyrosine antibody followed by Western blotting to determine the concentration of the tyrosine-nitrated protein.

Results

Expression of SERCA2 was significantly lower in patients with low BMI (4.2 [0.5] vs 8.1 [1.2] integrated optical density units, P<.05). SERCA2 was also tyrosine-nitrated in the patients with low BMI. Finally, a significant negative correlation was observed between the concentration of SERCA2 and that of inducible nitric oxide synthase (determined in a previous study using the same biopsy material) in patients with COPD and low BMI (r=0.89, P=.007), while such a correlation was not observed in patients with COPD and normal BMI (r=0.35, P=.43).

Conclusions

In patients with COPD, SERCA2 concentration is reduced and the protein is tyrosinenitrated in skeletal muscle from patients with low BMI compared to those with normal BMI. These results indicate the presence of a previously unrecognized cellular alteration in skeletal muscle from patients with COPD and low muscle weight.

Key words:
Cachexia
Chronic bronchitis
Emphysema
Smoking
Objetivo

Determinar las concentraciones y el estado de nitrosinación de SERCA2 (adenosintrifosfatasa de calcio del retículo sarcoplásmico) en biopsias del cuádriceps femoral de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) e índice de masa corporal (IMC) normal o bajo.

Pacientes y métodos

Los pacientes se distribuyeron en 2 grupos (n = 7) según su IMC fuera normal (> 21 kg/m2) o bajo (< 21 kg/m2). En ambos grupos se realizó una espirome-tría forzada, se determinó la concentración de gases en san-gre y se efectuaron biopsias percutáneas de aguja de la porción lateral del cuádriceps femoral. En estas biopsias se determinó la concentración de SERCA2 mediante inmunotransferencia y se evaluó si se encontraba nitrosinada mediante inmunoprecipitación de SERCA2 con un anticuerpo antinitrotirosina y posterior determinación de la concentración de SERCA2 nitrosinada mediante inmunotransferencia.

Resultados

La expresión de SERCA2 era significativa-mente inferior en los pacientes con IMC bajo (4,2 ± 0,5 fren-te a 8,1 ± 1,2 IOD; p < 0,05). En estos pacientes, además, SERCA2 se encontraba nitrosinada. Por último, se observó una relación negativa y significativa entre los valores de SERCA2 y las concentraciones de la óxido nítrico sintetasa inducible (tomadas de un trabajo anterior realizado con las mismas biopsias) en pacientes con EPOC y bajo peso corporal (r = -0,89; p = 0,007), relación que no existía en pacientes con EPOC e IMC normal (r = 0,35; p = 0,43).

Conclusiones

SERCA2 se encuentra disminuida y nitrosinada en el músculo esquelético de los pacientes con EPOC y bajo peso corporal, comparados con aquéllos con peso normal. Esta observación señala una nueva alteración celu-lar en el músculo esquelético de los pacientes con EPOC y bajo peso muscular.

Palabras clave:
Caquexia
Bronquitis crónica
Enfisema
Tabaco
Full text is only aviable in PDF
REFERENCES
[1]
Thoracic Society and European Respiratory Society.
Skeletal muscle dysfunction in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 159 (1999), pp. S1-S40
[2]
C Landbo, E Prescott, P Lange, J Vestbo, TP Almdal.
Prognostic value of nutritional status in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 160 (1999), pp. 1856-1861
[3]
AM Schols, J Slangen, L Volovics, EF Wouters.
Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 157 (1998), pp. 1791-1797
[4]
AG Agustí, A Noguera, J Sauleda, E Sala, J Pons, X Busquets.
Systemic effects of chronic obstructive pulmonary disease.
Eur Respir J, 21 (2003), pp. 347-360
[5]
R Debigare, CH Cote, F Maltais.
Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms.
Am J Respir Crit Care Med, 164 (2001), pp. 1712-1717
[6]
ME Kirtley, C Sumbilla, G Inesi.
Mechanisms of calcium uptake and release by sarcoplasmic reticulum.
Intracellular calcium regulation, pp. 543-564
[7]
M Aubier, N Viires.
Calcium ATPase and respiratory muscle function.
Eur Respir J, 11 (1998), pp. 758-766
[8]
A Agustí, M Morla, J Sauleda, C Saus, X Busquets.
NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight.
Thorax, 59 (2004), pp. 483-487
[9]
E Barreiro, J Gea, JM Corominas, SN Hussain.
Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease.
Am J Respir Cell Mol Biol, 29 (2003), pp. 771-778
[10]
C Astier, E Rock, C Lab, E Gueux, A Mazur, Y Rayssiguier.
Functional alterations in sarcoplasmic reticulum membranes of magnesium-deficient rat skeletal muscle as consequences of free radical-mediated process.
Free Radic Biol Med, 20 (1996), pp. 667-674
[11]
RF Castilho, PC Carvalho-Alves, AE Vercesi, ST Ferreira.
Oxidative damage to sarcoplasmic reticulum Ca(2+)-pump induced by Fe2+/H2O2/ascorbate is not mediated by lipid peroxidation or thiol oxidation and leads to protein fragmentation.
Mol Cell Biochem, 159 (1996), pp. 105-114
[12]
AK Grover, CY Kwan, SE Samson.
Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCA2b and SERCA3a.
Am J Physiol Cell Physiol, 285 (2003), pp. C1537-C1543
[13]
M Meyer, W Schillinger, B Pieske, C Holubarsch, C Heilmann, H Posival, et al.
Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy.
Circulation, 92 (1995), pp. 778-784
[14]
BR Celli, W MacNee, AG Agustí, A Anzueto, B Berg, AS Buist, et al.
Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.
Eur Respir J, 23 (2004), pp. 932-946
[15]
AG Agustí, J Sauleda, C Miralles, C Gómez, B Togores, E Sala, et al.
Skeletal muscle apoptosis and weight loss in chronicobstructive pulmonary disease.
Am J Respir Crit Care Med, 166 (2002), pp. 485-489
[16]
American Thoracic Society Official Statement.
Standardization of spirometry. 1994 Update.
Am J Respir Crit Care Med, 152 (1994), pp. 1107-1136
[17]
J Roca, J Sanchis, A Agustí-Vidal, F Segarra, D Navajas, R Rodríguez-Roisin, et al.
Spirometric reference values from a Mediterranean population.
Bull Eur Physiopathol Respir, 22 (1986), pp. 217-224
[18]
V Dubowitz, MH Brooke.
The procedure of muscle biopsy.
Muscle Biopsy: A Modern Approach, pp. 5-19
[19]
MA Bradford.
A rapid sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein dye-binding.
Anal Biochem, 72 (1976), pp. 248-252
[20]
E Zador, L Mendler, M Ver Heyen, L Dux, F Wuytack.
Changes in mRNA levels of the sarcoplasmic/endoplasmic-reticulum Ca(2+) ATPase isoforms in the rat soleus muscle regenerating from notexin-induced necrosis.
Biochem J, 320 (1996), pp. 107-113
[21]
A Simonini, K Chang, P Yue, CS Long, BM Massie.
Expression of skeletal muscle sarcoplasmic reticulum calcium-ATPase is reduced in rats with postinfarction heart failure.
Heart, 81 (1999), pp. 303-307
[22]
L Schulte, D Peters, J Taylor, J Navarro, S Kandarian.
Sarcoplasmic reticulum Ca2+ pump expression in denervated skeletal muscle.
Am J Physiol, 267 (1994), pp. C617-C622
[23]
HR Gosker, MP Engelen, H van Mameren, PJ van Dijk, GJ van der Vusse, EF Wouters, et al.
Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease.
Am J Clin Nutr, 76 (2002), pp. 113-119
[24]
HJ Green, CS Ballantyne, JD Mac Dougall, MA Tarnopolsky, JD Schertzer.
Adaptations in human muscle sarcoplasmic reticulum to prolonged submaximal training.
J Appl Physiol, 94 (2003), pp. 2034-2042
[25]
BB Friday, PO Mitchell, KM Kegley, GK Pavlath.
Calcineurin initiates skeletal muscle differentiation by activating MEF2 and MyoD.
Differentiation, 71 (2003), pp. 217-227
[26]
Y Liu, T Shen, WR Randall, MF Schneider.
Signaling pathways in activity-dependent fiber type plasticity in adult skeletal muscle.
J Muscle Res Cell Motil, 26 (2005), pp. 13-21
[27]
TJ Hawke, SB Kanatous, CM Martin, SC Goetsch, DJ Garry.
Rad is temporally regulated within myogenic progenitor cells during skeletal muscle regeneration.
Am J Physiol Cell Physiol, 290 (2006), pp. C379-C387

This study was funded in part by ABEMAR, the Spanish Ministry of Health Research Fund (FIS, PI 020978), Red Respira (RTIC C03/11), and the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR).

Copyright © 2007. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?