Barreiro Esther, Gea Joaquim
Pulmonology Department, IMIM-Hospital del Mar, PRBB, Dr. Aiguader, 88, E-08003 Barcelona, Spain.
Respiratory Medicine Department, Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
Biol Chem. 2018 Jan 26;399(2):179-186. doi: 10.1515/hsz-2017-0158.
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.
