Bladder cancer-induced skeletal muscle wasting: Disclosing the role of mitochondria plasticity

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• 作者：Ana Isabel Padrã ; o^a ; Paula Oliveira^b ; Rui Vitorino^a ; Bruno Colaç ; o^b ; Maria Joã ; o Pires^b ; Marcela Má ; rquez^c ; Enrique Castellanos^c ; Maria Joã ; o Neuparth^d ; Catarina Teixeira^a ; ^b ; Cé ; u Costa^e ; Daniel Moreira-Gonç ; alves^f ; Só ; nia Cabral^g ; José ; Alberto Duarte^f ; Lú ; cio Lara Santos^e ; ^g ; Francisco Amado^a ; ^h ; Rita Ferreira^a ; ^{ritaferreira@ua.pt}
• 关键词：Urothelial carcinoma ; Gastrocnemius wasting ; Mitochondrial proteolysis ; Protein quality control system
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：45
• 期：7
• 页码：1399-1409
• 全文大小：1487 K

文摘

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-1¦Â, TNF-¦Á, 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.