Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions.
OBJECTIVE
The aim of this overview is to highlight the multiple ways in which oxidative stress could be exacerbating muscle wasting. Understanding these interactions in vivo will assist in identifying opportunities for more targeted therapies to reduce skeletal muscle wasting.


RESULTS
There are many excellent reviews describing how oxidative stress can damage cellular macromolecules, as well as cause deleterious effects through the modulation of signalling pathways. In this overview, we highlight the potential for complex and possibly paradoxical interactions in vivo. Signalling pathways are discussed, using examples involving nuclear factor-kappa B, apoptosis signal-regulating kinase 1 and Akt. Oxidative stress may also be involved in complex interactions with other factors capable of stimulating the loss of muscle mass, possibly through amplifying feedback cycles. This is discussed using examples related to calcium and tumour necrosis factor.


CONCLUSIONS
There is convincing evidence that oxidative stress can increase protein catabolism. The challenge is to demonstrate that oxidative stress is a significant player in the complex interplay that leads to the in-vivo muscle wasting that is caused by a range of conditions and diseases.
School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, Crawley, Australia. parthur@cyllene.uwa.edu.au
Peter G
PG
Arthur
Miranda D
MD
Grounds
Thea
T
Shavlakadze
D002100:Cachexia / Q000209:etiology* / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology* / Q000517:prevention & control; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; D002118:Calcium