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Bladder cancer-induced skeletal muscle wasting: disclosing the role of mitochondria plasticity
- Source :
- The international journal of biochemistrycell biology. 45(7)
- Publication Year :
- 2012
-
Abstract
- Loss of skeletal muscle is a serious consequence of cancer as it leads to weakness and increased risk of death. To better understand the interplay between urothelial carcinoma and skeletal muscle wasting, cancer-induced catabolic profile and its relationship with muscle mitochondria dynamics were evaluated using a rat model of chemically induced urothelial carcinogenesis by the administration of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). The histologic signs of non-muscle-invasive bladder tumors observed in BBN animals were related to 17% loss of body weight and high serum levels of IL-1β, TNF-α, TWEAK, C-reactive protein, myostatin and lactate and high urinary MMPs activities, suggesting a catabolic phenotype underlying urothelial carcinoma. The 12% loss of gastrocnemius mass was related to mitochondrial dysfunction, manifested by decreased activity of respiratory chain complexes due to, at least partially, the impairment of protein quality control (PQC) systems involving the mitochondrial proteases paraplegin and Lon. This was paralleled by the accumulation of oxidatively modified mitochondrial proteins. In overall, our data emphasize the relevance of studying the regulation of PQC systems in cancer cachexia aiming to identify therapeutic targets to counteract muscle wasting.
- Subjects :
- Male
medicine.medical_specialty
Interleukin-1beta
Respiratory chain
Myostatin
Mitochondrion
Biochemistry
Internal medicine
medicine
Animals
Lactic Acid
Rats, Wistar
Muscle, Skeletal
Wasting
Bladder cancer
biology
Paraplegin
Tumor Necrosis Factor-alpha
Skeletal muscle
Cancer
Membrane Proteins
Cytokine TWEAK
Cell Biology
medicine.disease
Boronic Acids
Mitochondria, Muscle
Rats
Disease Models, Animal
Muscular Atrophy
Endocrinology
medicine.anatomical_structure
1-Naphthylamine
C-Reactive Protein
Urinary Bladder Neoplasms
Tumor Necrosis Factors
biology.protein
medicine.symptom
Urothelium
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 18785875
- Volume :
- 45
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- The international journal of biochemistrycell biology
- Accession number :
- edsair.doi.dedup.....76f85e40fb1a5f21e4654f854ea6d794