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Received February 9, 2006
Accepted on August 20, 2006

CLINICAL SCIENCE: Chronic Kidney Disease

Development of a Diagnostic Method for Detecting Increased Muscle Protein Degradation in Patients with Catabolic Conditions

Biruh T. Workeneh ^*, Helbert Rondon-Berrios ^*, Liping Zhang , Zhaoyong Hu , Gashu Ayehu ^*, Arny Ferrando ^*, Joel D. Kopple , Huiyun Wang , Thomas Storer ^||, Mario Fournier ^¶, Seoung Woo Lee ^*, Jie Du , and William E. Mitch ¹

*Medicine and Surgery, University of Texas Medical Branch, Galveston, and Nephrology Division, Baylor College of Medicine, Houston, Texas; Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and ||El Camino College, Torrance, California; David Geffen School of Medicine at UCLA and the UCLA School of Public Health and ¶Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California; and *Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University College of Medicine, Inchon City, Korea

¹ To whom correspondence should be addressed. E-mail: mitch{at}bcm.edu.

	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.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673