Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still Q4 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 glucocorticoidinduced 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 aetreated 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. (Am J Pathol 2013, -: 1e12; http://dx.doi.org/ 10.1016/j.ajpath.2012.12.023)

Autophagic degradation contributes to muscle wasting in cancer cachexia

PENNA, FABIO;COSTAMAGNA, DOMIZIANA;PIN, FABRIZIO;CAMPERI, ANDREA;CHIARPOTTO, Elena Maria;BONELLI, Gabriella;BACCINO, Francesco Maria;COSTELLI, Paola
2013

Abstract

Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still Q4 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 glucocorticoidinduced 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 aetreated 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. (Am J Pathol 2013, -: 1e12; http://dx.doi.org/ 10.1016/j.ajpath.2012.12.023)
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F. Penna; D. Costamagna; F. Pin; A. Camperi; A. Fanzani; E.M. Chiarpotto; G. Cavallini; G. Bonelli; F.M. Baccino; P. Costelli
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/130146
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