Increased Muscle Proteasome Activity Correlates With Disease Severity in Gastric Cancer Patients

摘要: Loss of lean body mass is commonly observed in cancer as well other catabolic conditions such sepsis, burns, severe injury, and renal failure. The progressive muscle wasting may have a negative impact on both the quality life tolerance to antineoplastic therapies, accounting for one two thirds deaths patients. 1,2 Muscle depletion reflects an imbalance between rates protein synthesis breakdown. Studies performed experimental models human shown that atrophy result from increased degradation, reduced synthesis, or both. However, hypercatabolism frequent feature, while changes seem occur less frequently. 3 Intracellular degradation skeletal depends several proteolytic systems: acidic lysosomal pathway, calcium-dependent ATP-ubiquitin-dependent pathway. 4 role played by systems onset does not be crucial. Recently, however, proteases been proposed required initial myofibrillar proteins 5 found activated tumor-bearing rats. 6 Upregulation components pathway has reported trauma, failure, acidosis, cancer. 7–14 Overexpression ubiquitin mRNA closely parallels enhancement rats bearing Yoshida AH-130 ascites hepatoma. 11 Moreover, treatment hosts with agents able block tissue hypercatabolism, anti-TNF antibodies clenbuterol, also reduces levels. 12,14 Modulations ubiquitin-proteasome documented patients suffering AIDS, 14–17 The proteolysis involves enzymatic cascade which multiple molecules are covalently attached substrate, then degraded 26S proteasome complex. catalytic core 20S proteasome, characterized five peptidase activities: trypsin-like (TL), chymotrypsin-like (CTL), peptidyl-glutamyl (PGP), branched-chain amino acid- preferring, small neutral acid-preferring activities. 18 The aim present study was investigate state activation system gastric results show cleavage specific fluorogenic substrates respect controls, indicating activity significantly enhanced hosts.