Disease relevance of CTSD

• Cathepsin D deficiency is associated with a human neurodegenerative disorder [1].
• Female lambs treated with TBA or zeranol showed increased weight gain, improved food conversion efficiency, decreased muscle RNA and DNA concentrations and decreased free cathepsin D activity in muscle [2].

High impact information on CTSD

• Two missense mutations in the CTSD gene, F229I and W383C, were identified and were found to cause markedly reduced proteolytic activity and a diminished amount of cathepsin D in patient fibroblasts [1].
• Cathepsin D is a ubiquitously expressed lysosomal protease that is involved in proteolytic degradation, cell invasion, and apoptosis [1].
• Moreover, the cathepsin D inhibitor, pepstatin A, did not prevent stress-induced cell death in human fibroblasts or lymphoblasts [3].
• Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, and CTSZ genes was detected in the endometria of cyclic and early pregnant ewes with distinct temporal and spatial expression patterns [4].
• On the other hand, over 80% of the GB111 phagosomes were similar to the AA100 phagosome in that they were devoid of LAMP-1 and cathepsin D, and they were colocalized with the endoplasmic reticulum (ER) marker BiP [5].

Biological context of CTSD

• Likewise the upregulation of cathepsin-D indicated increased lysosomal activity and HSC activation [6].
• The activity of cathepsin D increased significantly after the endocytosis of a heterologous protein [7].
• Peritoneal macrophages prepared from ethanol treated rats had lower phagocytosis via the Fe-receptor and reduced viability in the presence of endotoxin, but their lysosomal enzyme activities measured (beta-glucuronidase, cathepsin D, acid phosphatase and acid DNase) were not different from controls [8].
• On the basis of the present data, and the nearly identical clinical and/or pathological phenotype of the other reported cases of congenital NCL, it is reasonable to suggest that cathepsin D deficiency caused by mutations in the corresponding gene may underlie all cases of congenital NCL [9].

Anatomical context of CTSD

• Expression of cathepsin D mutants in cathepsin D(-/-) mouse fibroblasts revealed disturbed posttranslational processing and intracellular targeting for W383C and diminished maximal enzyme velocity for F229I [1].
• In the cell lines derived from these tissues, cathepsin D functions as an autocrine mitogen, and it was suggested that its secretion might pose some physiological functions [10].
• The concentrations of ubiquitin and cathepsin D mRNA in the rumen and jejunum were not modified by feeding level, demonstrating that the expression of these genes for proteolytic enzymes was unchanged under these conditions [11].
• Cellular heterogeneity in cathepsin D distribution in equine articular cartilage [12].
• Cathepsin D was absent in the hypertrophic zone of the distal radial growth plate [12].

Associations of CTSD with chemical compounds

• The possible role of lysosomal ceramide or sphingosine-mediated activation of cathepsin D in apoptosis was also excluded by using human cells either overexpressing or deficient in acid ceramidase [3].
• The latter were derived by tryptic, chymotryptic or cathepsin D digestion of the intact molecule and fractionated by DE-cellulose chromatography and gelatin and/or heparin affinity chromatography [13].
• Tissue composition and skeletal muscle cathepsin D (EC 3.4.23.5) activity were measured in wether lambs treated with trenbolone acetate (TBA) and oestradiol-17 beta (Oe) in combination and female lambs treated with TBA or zeranol [2].

Analytical, diagnostic and therapeutic context of CTSD

• By Western blotting, a 5-10 fold increase in the level of cathepsin D was confirmed [14].
• Cathepsin D was localised by immunofluorescence within four different types of cells derived from human trophoblast in monolayer culture [15].
• Despite the lack of cathepsin D activity, the brains of the cathepsin D deficient sheep showed strongly increased staining for cathepsin D in immunohistochemistry [14].

References