title: Bladder cancer-induced skeletal muscle wasting: disclosing the role of mitochondria plasticity.
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.
authors.affiliation: QOPNA, Chemistry Department, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Padrão
authors.forename: Paula
authors.initials: P
authors.lastname: Oliveira
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
authors.forename: Bruno
authors.initials: B
authors.lastname: Colaço
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pires
authors.forename: Marcela
authors.initials: M
authors.lastname: Márquez
authors.forename: Enrique
authors.initials: E
authors.lastname: Castellanos
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Neuparth
authors.forename: Catarina
authors.initials: C
authors.lastname: Teixeira
authors.forename: Céu
authors.initials: C
authors.lastname: Costa
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreira-Gonçalves
authors.forename: Sónia
authors.initials: S
authors.lastname: Cabral
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000097:blood; D001897:Boronic Acids; D002097:C-Reactive Protein / Q000032:analysis; D000074049:Cytokine TWEAK; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism*; D055435:Myostatin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048069:Tumor Necrosis Factors / Q000097:blood; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D001897:Boronic Acids; D000074049:Cytokine TWEAK; D053583:Interleukin-1beta; D008565:Membrane Proteins; D055435:Myostatin; C506447:N-(o-boronic acid)benzyl-1-naphthylamine; C497771:Tnfsf12 protein, rat; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019344:Lactic Acid; D002097:C-Reactive Protein; D015057:1-Naphthylamine