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Muscle wasting associated with cancer cachexia is linked to an important activation of the atp‐dependent ubiquitin‐mediated proteolysis
Author(s) -
Llovera Marta,
GarciaMartinez Cèlia,
Agell Neus,
LopezSoriano Francisco J.,
Argiles Josep M.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910610123
Subject(s) - proteases , proteolysis , cachexia , biochemistry , skeletal muscle , ubiquitin , endocrinology , biology , medicine , chemistry , enzyme , cancer , gene
Rats bearing the Yoshida AH‐130 ascites hepatoma for 7 days showed an important decrease in muscle mass—over 30% in gastrocnemius and extensor digitorum longus (EDL)—in relation to non‐tumour‐bearing controls, which is associated with an increased proteolytic rate‐in in vitro incubation. In order to identify the precise biochemical process which was involved, we measured different proteolytic systems in incubated EDL muscles. The capacity for intralysosomal proteolysis, as measured by sensitivity to methylamine, was not increased in tumour‐bearing rats, suggesting that the mechanism involved in the increased proteolytic rate was extralysosomal. Incubations using the Ca 2+ ionophore A23187 revealed no change in the activity of calcium‐dependent proteases as a consequence of tumour growth. Finally, muscle incubation in an ATP‐depleted medium allowed us to conclude that energy‐dependent proteases were involved in the activation of muscle proteolysis in tumour‐bearing rats. In particular, the ubiquitin‐dependent proteolytic system is involved, since there is an important increase in ubiquitin conjugates in the skeletal muscle of tumour‐bearing rats. It may thus be suggested that extralysosomal ATP‐and ubiquitin‐dependent proteases underlie the biochemical mechanism of muscle wastage associated with cancer cachexia. © 1995 Wiley‐Liss, Inc .