Both oxidative and nitrosative stress are associated with muscle wasting in tumour‐bearing rats

FEBS Letters - Tập 579 - Trang 1646-1652 - 2005
Esther Barreiro1, Beatriz de la Puente1, Sílvia Busquets2, Francisco J. López-Soriano2, Joaquim Gea1,3, Josep M. Argilés2
1Muscle and Respiratory System Research Unit, IMIM and CEXS, Universitat Pompeu Fabra, Barcelona, Spain
2Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain
3Respiratory Medicine Department, Hospital del Mar, Barcelona, Spain

Tóm tắt

Reactive oxygen and nitrogen species (ROS and RNS) have been proposed as mechanisms of cancer‐induced cachexia. In this study, we assessed using Western blot analysis the levels of total protein carbonylation (2,4‐dinitrophenylhydrazine assay), both malondialdehyde‐ (MDA‐) and 2‐hydroxy‐4‐nonenal‐ (HNE‐) protein adducts, Mn‐superoxide dismutase (Mn‐SOD), catalase, heme oxygenase‐1 (HO‐1) and 3‐nitrotyrosine formation in gastrocnemius muscles of rats bearing the Yoshida AH‐130 hepatoma. In the muscles of the tumour‐bearing animals, protein carbonylation as measured by total levels of carbonyl group formation and both HNE and MDA‐protein adducts, and protein tyrosine nitration were significantly greater than in control muscles. Protein levels of the antioxidant enzymes Mn‐SOD, catalase, and HO‐1 were not significantly modified in the rat cachectic muscles compared to controls. The inefficiency of the antioxidant enzymes in neutralizing excessive ROS production may account for elevated markers of protein oxidation and be responsible for the development of both oxidative and nitrosative stress in cancer‐induced cachexia.

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