title: Autophagic degradation contributes to muscle wasting in cancer cachexia.
abstract: Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still unclear, although the ubiquitin-proteasome system has been involved in the degradation of bulk myofibrillar proteins. The present work has been aimed to investigate whether autophagic degradation also plays a role in the onset of muscle depletion in cancer-bearing animals and in glucocorticoid-induced atrophy and sarcopenia of aging. The results show that autophagy is induced in muscle in three different models of cancer cachexia and in glucocorticoid-treated mice. In contrast, autophagic degradation in the muscle of sarcopenic animals is impaired but can be reactivated by calorie restriction. These results further demonstrate that different mechanisms are involved in pathologic muscle wasting and that autophagy, either excessive or defective, contributes to the complicated network that leads to muscle atrophy. In this regard, particularly intriguing is the observation that in cancer hosts and tumor necrosis factor α-treated C2C12 myotubes, insulin can only partially blunt autophagy induction. This finding suggests that autophagy is triggered through mechanisms that cannot be circumvented by using classic upstream modulators, prompting us to identify more effective approaches to target this proteolytic system.
authors: Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy.
authors: Fabio
authors: F
authors: Penna
authors: Domiziana
authors: D
authors: Costamagna
authors: Fabrizio
authors: F
authors: Pin
authors: Andrea
authors: A
authors: Camperi
authors: Alessandro
authors: A
authors: Fanzani
authors: Elena M
authors: EM
authors: Chiarpotto
authors: Gabriella
authors: G
authors: Cavallini
authors: Gabriella
authors: G
authors: Bonelli
authors: Francesco M
authors: FM
authors: Baccino
authors: Paola
authors: P
authors: Costelli
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002100:Cachexia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D003720:Densitometry; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009132:Muscles / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000150:complications / Q000235:genetics / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019282:Wasting Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology*
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha