Advanced

Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia : altered energetic efficiency?

Fontes-Oliveira, Cibely Cristine LU ; Busquets, Sílvia; Toledo, Míriam; Penna, Fabio; Paz Aylwin, Maria; Sirisi, Sònia; Silva, Ana Paula; Orpí, Marcel; García, Albert and Sette, Angelica, et al. (2013) In Biochimica et biophysica acta 1830(3). p.8-2770
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... (More)

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.

GENERAL SIGNIFICANCE: 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.

(Less)
Please use this url to cite or link to this publication:
@article{43929307-d79a-4a5c-8192-1b683f5090d9,
  abstract     = {<p>BACKGROUND: Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass.</p><p>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.</p><p>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.</p><p>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.</p><p>GENERAL SIGNIFICANCE: 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.</p>},
  author       = {Fontes-Oliveira, Cibely Cristine and Busquets, Sílvia and Toledo, Míriam and Penna, Fabio and Paz Aylwin, Maria and Sirisi, Sònia and Silva, Ana Paula and Orpí, Marcel and García, Albert and Sette, Angelica and Inês Genovese, Maria and Olivan, Mireia and López-Soriano, Francisco J and Argilés, Josep M},
  issn         = {0006-3002},
  keyword      = {Adenine Nucleotide Translocator 1,Adenosine Triphosphate,Animals,Apoptosis,Cachexia,Cell Nucleus,Energy Metabolism,Gene Expression,Male,Mitochondria,Muscle Proteins,Muscle, Skeletal,Muscular Atrophy,Proteolysis,Rats,Rats, Wistar,SKP Cullin F-Box Protein Ligases,Sarcoma, Yoshida,Sarcoplasmic Reticulum,Sarcoplasmic Reticulum Calcium-Transporting ATPases,Tripartite Motif Proteins,Ubiquitin-Protein Ligases,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {8--2770},
  publisher    = {Elsevier},
  series       = {Biochimica et biophysica acta},
  title        = {Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia : altered energetic efficiency?},
  url          = {http://dx.doi.org/10.1016/j.bbagen.2012.11.009},
  volume       = {1830},
  year         = {2013},
}