Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of of protein degradation in muscle changes in many states but the nature of these changes is often paradoxical. Thus there can be increases during growth (anabolic increases) as well as during wasting (catabolic increases). Decreases can occur during growth (anabolic decreases) as well as during wasting (catabolic decreases). These changes are observed in man (as judged by changes in 3-methylhistidine excretion) and in experimental animals. The nature of the changes is not understood but it is possible that muscle growth induces increased degradation as part of the accompanying myofibre remodelling. The rate of protein degradation can also be influenced by thyroid status, since in thyroid deficiency degradation is reduced and can be stimulated by triiodothyronine. This response is independent of changes in muscle growth. Finally, acute exercise suppresses protein degradation in vivo in man as well as suppressing protein synthesis (in vivo in rats). When protein degradation rates change, acid proteinase activities also change in muscle. The anabolic increase in degradation appears to involve increases in mainly cathepsin D whereas catabolic increases in degradation are associated with an increase mainly in pepstatin-insensitive acid autolytic activity.
 ...
PMID:Protein degradation and the regulation of protein balance in muscle. 39 93

Protein degradation was measured as tyrosine release rate from proteins of extensor digitorum longus (EDL) muscles and as urinary excretion of 3-methylhistidine in freely fed adult nongrowing C57BL/6J mice with sarcomas, to study protein degradation in cancer-induced wasting of skeletal muscles. Whole muscle protein breakdown rate was unchanged, whereas protein synthesis was depressed, leading to an increased net degradation of skeletal muscles with loss of soluble, myofibrillar, and collagen proteins. Starvation for 24 hours elevated whole muscle protein breakdown in mice with and without sarcomas. Subsequent refeeding for 24 hours normalized the degradation. Adaptation to anorexia in pair-fed controls was achieved by a decrease in muscle protein turnover evaluated by urinary excretion of 3-methylhistidine over 5 days. The measurement of "catabolic decrease" of muscle protein breakdown protected the muscle mass in mice without tumors, but it was ineffective in tumor-bearing animals. The unchanged rate of breakdown of proteins in whole EDL muscles from tumor-bearing mice was accompanied by increased maximum cathepsin D activity and by elevated autolytic activity at acid pH in some muscles. Therefore, cathepsin D activity and net protease activities did not reflect whole muscle protein degradation in tumor-induced malnutrition. The results demonstrate that wasting of skeletal muscles in experimental cancer was not dependent on increased degradation but was dependent on depressed protein synthesis.
 ...
PMID:Lack of evidence for elevated breakdown rate of skeletal muscles in weight-losing, tumor-bearing mice. 657 91

The cellular mechanisms responsible for enhanced muscle protein breakdown in hospitalized patients, which frequently results in lean body wasting, are unknown. To determine whether the lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways are activated, we measured mRNA levels for components of these processes in muscle biopsies from severe head trauma patients. These patients exhibited negative nitrogen balance and increased rates of whole-body protein breakdown (assessed by [13C]leucine infusion) and of myofibrillar protein breakdown (assessed by 3-methylhistidine urinary excretion). Increased muscle mRNA levels for cathepsin D, m-calpain, and critical components of the ubiquitin proteolytic pathway (i.e., ubiquitin, the 14-kDa ubiquitin-conjugating enzyme E2, and proteasome subunits) paralleled these metabolic adaptations. The data clearly support a role for multiple proteolytic processes in increased muscle proteolysis. The ubiquitin proteolytic pathway could be activated by altered glucocorticoid production and/or increased circulating levels of interleukin 1beta and interleukin 6 observed in head trauma patients and account for the breakdown of myofibrillar proteins, as was recently reported in animal studies.
 ...
PMID:Increased mRNA levels for components of the lysosomal, Ca2+-activated, and ATP-ubiquitin-dependent proteolytic pathways in skeletal muscle from head trauma patients. 861 Jan 6