Open AccessDevelopment of a Diagnostic Method for Detecting Increased Muscle Protein Degradation in Patients with Catabolic Conditions
Author(s) -
Biruh Workeneh,
Helbert RondonBerrios,
Liping Zhang,
Zhaoyong Hu,
Gashu Ayehu,
Arny A. Ferrando,
Joel D. Kopple,
Huiyun Wang,
Thomas W. Storer,
Mario Fournier,
Seoung Woo Lee,
Jie Du,
William E. Mitch
Publication year - 2006
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2006020131
Subject(s) - proteolysis , myofibril , catabolism , protein degradation , actin , protein catabolism , muscle atrophy , medicine , skeletal muscle , endocrinology , proteasome , biochemistry , biology , enzyme , metabolism , amino acid
Muscle atrophy in catabolic illnesses is due largely to accelerated protein degradation. Unfortunately, methods for detecting accelerated muscle proteolysis are cumbersome. The goal of this study was to develop a method for detecting muscle protein breakdown and assess the effectiveness of anticatabolic therapy. In rodent models of catabolic conditions, it was found that accelerated muscle protein degradation is triggered by activation of caspase-3. Caspase-3 cleaves actomyosin/myofibrils to form substrates for the ubiquitin-proteasome system and leaves a characteristic 14-kD actin fragment in the insoluble fraction of a muscle lysate. Muscle biopsies were obtained from normal adults and three groups of patients: 14 who were undergoing hip arthroplasty, 28 hemodialysis patients who were participating in exercise programs, and seven severely burned patients. In muscle of patients who were undergoing hip arthroplasty, the 14-kD actin fragment level was correlated (r = 0.787, P < 0.01) with the fractional rate of protein degradation. In muscle of hemodialysis patients who were undergoing endurance exercise training, the 14-kD actin fragment decreased to values similar to levels in normal adults; strength training did not significantly decrease the actin fragment. Severely burned patients had increased muscle protein degradation and actin fragment levels, but the two measures were not significantly correlated. The experimental results suggest that the 14-kD actin fragment in muscle biopsies is increased in catabolic states and could be used in conjunction with other methods to detect and monitor changes in muscle proteolysis that occur in patients with mild or sustained increases in muscle proteolysis.