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)

Because protein degradation in liver and skeletal muscle is increased by thyroid hormones and decreased by thyroidectomy; we investigated the influence of thyroid hormones on the level of lysosomal enzymes. Hypophysectomized rats received daily injections of L-thyroxine or L-triiodothyronine. After 3 days of this regimen, homogenates of liver and skeletal muscle showed a 2- to 3-fold increase in the activities of cathepsin D, cathepsin B, and other lysosomal enzymes including leucine aminopeptidase, acid phosphatase, beta-galactosidase, N-acetylglucosaminidase, and alpha-mannosidase. In liver, this effect reflected increased enzyme activity in the two subcellular fractions that normally contain lysosomes. Titration of cathepsin D with pepstatin indicated that the increase in this activity resulted from an increase in the number of enzyme molecules. These effects occurred with both pharmacologic (thyrotoxic) and physiologic (growth-promoting) doses of thyroid hormones. Liver and skeletal muscle from thyroidectomized rats had approximately 50% of the normal levels of lysosomal enzyme activities. Under these various conditions, heart and kidney, tissues in which protein degradation does not appear to be influenced by thyroid hormones, showed no significant changes in lysosomal hydrolases. Thus, thyroid hormones regulate proteolytic and other lysosomal enzyme activities in those tissues in which these hormones influence protein degradation. Many characteristic features of hyperthyroidism and hypothyroidism may result from changes in levels of lysosomal enzymes.
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PMID:Thyroid hormones control lysosomal enzyme activities in liver and skeletal muscle. 27 25

The purpose of this study was to determine whether or not alternations in tumor growth induced by changes in thyroid status were mediated through changes in key enzymes, whose activity is known to be influenced by thyroid hormones. The activities of three lysosomal enzymes (cathepsin B1, cathepsin D, and acid phosphatase) and thymidylate synthetase were measured in implanted mammary tumors as well as in the livers of host animals that were either euthyroid, hypothyroid, or hyperthyroid. Hypothyroidism produced no significant change in enzyme activity in the tumors. Hyperthyroidism, on the other hand, did cause a significant increase in the activity of all lysosomal enzymes in the tumors, but did not affect thymidylate synthetase levels. In the livers of the host animals, hypothyroidism produced a significant decrease in cathepsin B1 and a significant increase in acid phosphatase but did not change cathepsin D or thymidylate synthetase levels. Hyperthyroidism produced a significant increase in all enzymes measured in the livers of the host animals. The significant decrease in tumor weight with hypothyroidism did not correlate with the insignificant changes in the enzymes tested. Similarly, there was no correlation between the significant increase in the enzymes levels found with hyperthyroidism and the insignificant change in tumor weight.
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PMID:Effect of altered thyroid status on lysosomal enzymes and thymidylate synthetase activity in tumors and livers of host animals. 707 81