title: Development of a diagnostic method for detecting increased muscle protein degradation in patients with catabolic conditions.
abstract: 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.
authors.affiliation: Medicine and Surgery, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Biruh T
authors.initials: BT
authors.lastname: Workeneh
authors.forename: Helbert
authors.initials: H
authors.lastname: Rondon-Berrios
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.forename: Gashu
authors.initials: G
authors.lastname: Ayehu
authors.forename: Arny
authors.initials: A
authors.lastname: Ferrando
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kopple
authors.forename: Huiyun
authors.initials: H
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Storer
authors.forename: Mario
authors.initials: M
authors.lastname: Fournier
authors.forename: Seoung Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: William E
authors.initials: WE
authors.lastname: Mitch
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis
chemical_list: D000199:Actins; D009124:Muscle Proteins; D010446:Peptide Fragments; C033025:actin subfragments