title: Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: altered energetic efficiency?
abstract: BACKGROUND
  Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass.
  
  
  METHODS
  The Yoshida AH-130 tumor model has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR and Western blot techniques.
  
  
  RESULTS
  Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fiber morphologic alterations such as mitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca(2+)-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency, was observed. Tumor burden also leads to a marked decreased in muscle ATP content.
  
  
  CONCLUSIONS
  In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum-mitochondrial assembly that is essential for muscle function and homeostasis.
  
  
  CONCLUSIONS
  The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia.
authors.affiliation: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645 08028-Barcelona, Spain.
authors.forename: Cibely Cristine
authors.initials: CC
authors.lastname: Fontes-Oliveira
authors.forename: Sílvia
authors.initials: S
authors.lastname: Busquets
authors.forename: Míriam
authors.initials: M
authors.lastname: Toledo
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.forename: Maria
authors.initials: M
authors.lastname: Paz Aylwin
authors.forename: Sònia
authors.initials: S
authors.lastname: Sirisi
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Silva
authors.forename: Marcel
authors.initials: M
authors.lastname: Orpí
authors.forename: Albert
authors.initials: A
authors.lastname: García
authors.forename: Angelica
authors.initials: A
authors.lastname: Sette
authors.forename: Maria
authors.initials: M
authors.lastname: Inês Genovese
authors.forename: Mireia
authors.initials: M
authors.lastname: Olivan
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Soriano
authors.forename: Josep M
authors.initials: JM
authors.lastname: Argilés
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000172:deficiency; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002100:Cachexia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism / Q000235:genetics; D015870:Gene Expression; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D051381:Rats; D017208:Rats, Wistar; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D012517:Sarcoma, Yoshida / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D033741:Adenine Nucleotide Translocator 1; C506945:Atp2a1 protein, rat; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D000255:Adenosine Triphosphate; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases