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Reduced Expression of the Sarcoplasmic Calcium Pump SERCA2 in Skeletal Muscle From Patients With Chronic Obstructive Pulmonary Disease and Low Body Weight
Montse Morlàa, Amanda Iglesiasa, Jaume Sauledab, Borja Cosiob, Àlvar Agustía,b, Xavier Busquetsa,c,
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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
Correspondence: Dr. X. Busquets. Unidad de Investigación. Hospital Universitario Son Dureta (Edificio D, primera planta). Andrea Doria, 55. 07014 Palma de Mallorca. Baleares. España
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Busquets. Unidad de Investigación. Hospital Universitario Son Dureta (Edificio D, primera planta). Andrea Doria, 55. 07014 Palma de Mallorca. Baleares. España" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2005-10-07" "fechaAceptado" => "2006-03-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec154564" "palabras" => array:4 [ 0 => "Cachexia" 1 => "Chronic bronchitis" 2 => "Emphysema" 3 => "Smoking" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec154565" "palabras" => array:4 [ 0 => "Caquexia" 1 => "Bronquitis crónica" 2 => "Enfisema" 3 => "Tabaco" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">To compare the concentrations and extent of nitration of sarcoplasmic-endoplasmic reticulum Ca<span class="elsevierStyleSup">2+</span> 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).</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">The patients were divided into 2 groups (n=7, each group), one containing individuals with normal BMI (>21 kg/m<span class="elsevierStyleSup">2</span>) and the other with low BMI (<21 kg/m<span class="elsevierStyleSup">2</span>). 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.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">Expression of SERCA2 was significantly lower in patients with low BMI (4.2 [0.5] vs 8.1 [1.2] integrated optical density units, <span class="elsevierStyleItalic">P</span><.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 (<span class="elsevierStyleItalic">r</span>=0.89, <span class="elsevierStyleItalic">P</span>=.007), while such a correlation was not observed in patients with COPD and normal BMI (<span class="elsevierStyleItalic">r</span>=0.35, <span class="elsevierStyleItalic">P</span>=.43).</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Pacientes y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Los pacientes se distribuyeron en 2 grupos (n = 7) según su IMC fuera normal (> 21 kg/m<span class="elsevierStyleSup">2</span>) o bajo (< 21 kg/m<span class="elsevierStyleSup">2</span>). 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.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">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).</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara">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).</p>" ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skeletal muscle dysfunction in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Thoracic Society and European Respiratory Society" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.159.supplement_1.99titlepage" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1999" "volumen" => "159" "paginaInicial" => "S1" "paginaFinal" => "S40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10194189" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic value of nutritional status in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C Landbo" 1 => "E Prescott" 2 => "P Lange" 3 => "J Vestbo" 4 => "TP Almdal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.160.6.9902115" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1999" "volumen" => "160" "paginaInicial" => "1856" "paginaFinal" => "1861" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10588597" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "AM Schols" 1 => "J Slangen" 2 => "L Volovics" 3 => "EF Wouters" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.157.6.9705017" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1998" "volumen" => "157" "paginaInicial" => "1791" "paginaFinal" => "1797" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9620907" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic effects of chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "AG Agustí" 1 => "A Noguera" 2 => "J Sauleda" 3 => "E Sala" 4 => "J Pons" 5 => "X Busquets" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2003" "volumen" => "21" "paginaInicial" => "347" "paginaFinal" => "360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12608452" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peripheral muscle wasting in chronic obstructive pulmonary disease. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 2 | 5 |
| 2024 October | 27 | 20 | 47 |
| 2024 September | 30 | 17 | 47 |
| 2024 August | 50 | 29 | 79 |
| 2024 July | 26 | 19 | 45 |
| 2024 June | 26 | 29 | 55 |
| 2024 May | 45 | 36 | 81 |
| 2024 April | 20 | 20 | 40 |
| 2024 March | 22 | 15 | 37 |
| 2024 February | 17 | 20 | 37 |
| 2023 March | 2 | 0 | 2 |
| 2023 February | 13 | 25 | 38 |
| 2023 January | 17 | 39 | 56 |
| 2022 December | 24 | 37 | 61 |
| 2022 November | 24 | 30 | 54 |
| 2022 October | 25 | 31 | 56 |
| 2022 September | 12 | 20 | 32 |
| 2022 August | 17 | 37 | 54 |
| 2022 July | 22 | 36 | 58 |
| 2022 June | 11 | 33 | 44 |
| 2022 May | 15 | 41 | 56 |
| 2022 April | 22 | 40 | 62 |
| 2022 March | 13 | 38 | 51 |
| 2022 February | 13 | 35 | 48 |
| 2022 January | 15 | 28 | 43 |
| 2021 December | 11 | 43 | 54 |
| 2021 November | 12 | 56 | 68 |
| 2021 October | 25 | 47 | 72 |
| 2021 September | 13 | 61 | 74 |
| 2021 August | 9 | 23 | 32 |
| 2021 July | 13 | 25 | 38 |
| 2021 June | 15 | 29 | 44 |
| 2021 May | 17 | 17 | 34 |
| 2021 April | 28 | 36 | 64 |
| 2021 March | 19 | 10 | 29 |
| 2021 February | 11 | 19 | 30 |
| 2021 January | 10 | 10 | 20 |
| 2020 December | 9 | 6 | 15 |
| 2020 November | 8 | 10 | 18 |
| 2020 October | 8 | 5 | 13 |
| 2020 September | 2 | 2 | 4 |
| 2020 August | 10 | 8 | 18 |
| 2020 July | 14 | 14 | 28 |
| 2020 June | 10 | 7 | 17 |
| 2020 May | 9 | 13 | 22 |
| 2020 April | 11 | 13 | 24 |
| 2020 March | 11 | 10 | 21 |
| 2020 February | 22 | 11 | 33 |
| 2020 January | 21 | 21 | 42 |
| 2019 December | 20 | 10 | 30 |
| 2019 November | 12 | 8 | 20 |
| 2019 October | 4 | 2 | 6 |
| 2019 September | 10 | 15 | 25 |
| 2019 August | 20 | 4 | 24 |
| 2019 July | 20 | 13 | 33 |
| 2019 June | 5 | 10 | 15 |
| 2019 May | 12 | 2 | 14 |
| 2019 April | 17 | 9 | 26 |
| 2019 March | 15 | 13 | 28 |
| 2019 February | 10 | 15 | 25 |
| 2019 January | 11 | 11 | 22 |
| 2018 December | 16 | 13 | 29 |
| 2018 November | 23 | 13 | 36 |
| 2018 October | 27 | 24 | 51 |
| 2018 September | 17 | 20 | 37 |
| 2018 May | 5 | 0 | 5 |
| 2018 April | 17 | 6 | 23 |
| 2018 March | 7 | 1 | 8 |
| 2018 February | 5 | 9 | 14 |
| 2018 January | 4 | 2 | 6 |
| 2017 December | 4 | 5 | 9 |
| 2017 November | 6 | 5 | 11 |
| 2017 October | 4 | 3 | 7 |
| 2017 September | 5 | 6 | 11 |
| 2017 August | 8 | 10 | 18 |
| 2017 July | 3 | 3 | 6 |
| 2017 June | 9 | 9 | 18 |
| 2017 May | 7 | 6 | 13 |
| 2017 April | 1 | 4 | 5 |
| 2017 March | 3 | 6 | 9 |
| 2017 February | 2 | 3 | 5 |
| 2017 January | 2 | 4 | 6 |
| 2016 December | 3 | 3 | 6 |
| 2016 November | 14 | 6 | 20 |
| 2016 October | 11 | 5 | 16 |
| 2016 September | 6 | 3 | 9 |
| 2016 August | 8 | 7 | 15 |
| 2016 July | 3 | 0 | 3 |
| 2016 March | 1 | 0 | 1 |
| 2016 February | 1 | 0 | 1 |
| 2015 December | 3 | 0 | 3 |
| 2015 October | 36 | 6 | 42 |
| 2015 September | 27 | 5 | 32 |
| 2015 August | 24 | 13 | 37 |
| 2015 July | 41 | 4 | 45 |
| 2015 June | 26 | 5 | 31 |
| 2015 May | 41 | 7 | 48 |
| 2015 April | 29 | 9 | 38 |
| 2015 March | 25 | 8 | 33 |
| 2015 February | 21 | 2 | 23 |
| 2015 January | 18 | 5 | 23 |
| 2014 December | 35 | 6 | 41 |
| 2014 November | 32 | 4 | 36 |
| 2014 October | 30 | 9 | 39 |
| 2014 September | 19 | 5 | 24 |
| 2014 August | 24 | 6 | 30 |
| 2014 July | 28 | 9 | 37 |
| 2014 June | 29 | 2 | 31 |
| 2014 May | 37 | 7 | 44 |
| 2014 April | 40 | 8 | 48 |
| 2014 March | 49 | 6 | 55 |
| 2014 February | 33 | 8 | 41 |
| 2014 January | 31 | 8 | 39 |
| 2013 December | 32 | 7 | 39 |
| 2013 November | 29 | 4 | 33 |
| 2013 October | 27 | 10 | 37 |
| 2013 September | 21 | 8 | 29 |
| 2013 August | 27 | 4 | 31 |
| 2013 July | 45 | 8 | 53 |
| 2013 June | 32 | 5 | 37 |
| 2013 May | 33 | 7 | 40 |
| 2013 April | 16 | 2 | 18 |
| 2013 March | 6 | 1 | 7 |
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