Cathepsin B and D activity in human skeletal muscle in disease states.
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Biomedical subjects
Publications and source records attributed to R Situlin.
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Malnutrition is a common finding in chronic pancreatitis and its pathogenesis is multifactorial. In 14 patients with chronic pancreatitis we assessed the dietary intake, some anthropometric indices and the concentration of some serum proteins. In muscle specimens obtained by needle biopsy we examined the DNA, RNA and non-collagen alkali-soluble protein (ASP) content. In muscle we determined also the activity of cathepsin D, an enzyme involved in intracellular myofibrillar catabolism. Protein and energy intake were lower than in the normal healthy population. Plasma protein content (an index of liver protein synthesis) was generally in the normal range, whereas anthropometry and the biochemical muscle indices were generally subnormal, suggesting a depressed muscle protein content and synthesis (evaluated, respectively, by the ASP: DNA and RNA: DNA ratios). Cathepsin D activity was lower than in controls, and the percentage of 'free' activity tended to be higher but not significantly. This study suggests that muscle protein content and synthesis are reduced in patients with chronic pancreatitis, whereas liver protein synthesis is generally preserved. Possibly as a consequence of metabolic abnormalities and/or of an inadequate protein and energy intake, the nutritional status was often abnormal in our patients and a nutritional support therapy was needed.
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Evidence for muscle protein wasting and abnormal muscle metabolism is common in uremia. Muscle DNA content is considered a reliable reference standard in normal and undernourished adults. Muscle RNA content rapidly changes during starvation and refeeding. The ratio of noncollagen alkali-soluble proteins (ASP) to DNA is considered to be an estimate of the cytoplasmic volume of a single cell, and the RNA: DNA ratio is an index of the ribosomal capacity for protein synthesis. Muscle DNA, RNA, ASP, water, and fat content were determined in muscle biopsy specimens from chronically uremic patients receiving conservative treatment (CT), maintenance hemodialysis (two centers), or CAPD. Nutrient intake was low and the anthropometric indices were decreased in all groups of patients, except in the hemodialysis patients from one center. Serum proteins and muscle ASP: DNA and RNA: DNA ratios were decreased. The nutritional status was reassessed in some malnourished CAPD patients after about one year of careful nutritional advice and was unchanged. These results suggest that chronically uremic patients on CT are often malnourished, primarily because of an inadequate protein and/or energy intake. Muscle nucleic acid and protein content are useful tools for nutritional assessment at a cellular level in humans with chronic renal failure and can be used to monitor the response to nutritional therapy.
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