Open AccessDecreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle
Author(s) -
Sullivan-Gunn Melanie J.,
Campbell-O'Sullivan Siun P.,
Tisdale Michael J.,
Lewandowski Paul A.
Publication year - 2011
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1007/s13539-011-0037-3
Subject(s) - sod2 , nadph oxidase , antioxidant , superoxide dismutase , skeletal muscle , endocrinology , superoxide , medicine , oxidative stress , chemistry , cachexia , reactive oxygen species , sod1 , biochemistry , enzyme , biology , cancer
Background Cancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour‐bearing cachectic mice. Methods Superoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples. Results Superoxide levels increased 1.4‐fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40 phox and p67 phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3‐fold decrease in SOD1 and 2.0‐fold decrease in GPx enzyme activity. Conclusion Despite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40 phox and p67 phox , were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.