Muscle wasting associated with cancer cachexia is linked to an important activation of the ATP-dependent ubiquitin-mediated proteolysis. 1995

M Llovera, and C Garcia-Martinez, and N Agell, and F J Lopez-Soriano, and J M Argiles
Departament de BioquĂ­mica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.

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 Ca2+ 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.

UI MeSH Term Description Entries
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008297 Male Males
D009124 Muscle Proteins The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN. Muscle Protein,Protein, Muscle,Proteins, Muscle
D009135 Muscular Diseases Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE. Muscle Disorders,Myopathies,Myopathic Conditions,Muscle Disorder,Muscular Disease,Myopathic Condition,Myopathy
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010447 Peptide Hydrolases Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES. Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D002100 Cachexia General ill health, malnutrition, and weight loss, usually associated with chronic disease.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations

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