Disease relevance of CTSD

• Plasma Cathepsin D activity was significantly elevated (26-fold above control) in the group with gram-negative septic shock as compared to all other groups [1].
• Pepstatin, a known inhibitor of cathepsin D, was infused into isolated guniea pig hearts (Langendorff preparation) in order to observe if such an administration of pepstatin would protect against the effects of a two minute exposure to hypoxia [2].
• Intracellular cathepsin D is thought to play a role in myocardial injury produced by ischemia and hypoxia [2].
• Animals haemorrhaged to produce sustained hypotension that was greater than the reduction in blood pressure seen with endotoxin treatment, exhibited an elevation only in plasma Cathepsin D activity that was, however, significantly lower than the increase associated with endotoxemia [1].
• We studied the effects of tamoxifen and chloroquine on the activity of the lysosomal enzymes N-acetyl-beta-glucosaminidase and cathepsin D in RPE in vitro to evaluate the possible eye toxicity caused by these drugs [3].

High impact information on CTSD

• Type II autophagic vacuoles, by contrast, are enriched for acid phosphatase, cathepsin D, and other lysosomal enzymes, and they are also enriched for CI-M6PR [4].
• Cathepsin D activity in the nuclear and mitochondrial-microsomal fractions was decreased if assays were done without prior treatment to rupture membranous structures; hence, our cell rupture and homogenization procedures preserved some intact lysosomal organelles [5].
• Using a nonbiased proteomic approach combining 2D gel electrophoresis with in-gel proteolysis, peptide mapping by MS, and sequence database searches for protein identification, we demonstrated increased expression of cathepsin D, a protein known to mediate autophagy [6].
• The partial clone was used to screen a size-selected human kidney cDNA library, from which two cathepsin D recombinant plasmids with inserts of about 2200 and 2150 base pairs were obtained [7].
• Poly(A)+ RNA blot analysis with this cathepsin D clone demonstrated a message length of about 2.2 kilobases [7].

Biological context of CTSD

• Amino acid sequence of porcine spleen cathepsin D [8].
• The active site aspartyl residues, corresponding to aspartic acid-32 and -215 of pepsin, are located at residues 33 and 224 in the cathepsin D molecule [8].
• A comparison of the substrate specificities of cathepsin D and pseudorenin [9].
• A computer-generated model of the cathepsin D/pepsinogen chimeric molecule served as a guide for mutagenesis and for the interpretation of results [10].
• The amino acid sequences near the glycosylation sites and the oligosaccharide structures have been determined for the lysosomal protease cathepsin D from porcine spleen [11].

Anatomical context of CTSD

• A hybrid molecule (H6), in which the propiece and first 12 amino acids of proteinase A were changed to the cathepsin D sequence, was also expressed in oocytes [12].
• Cathepsin D isozymes from porcine spleens. Large scale purification and polypeptide chain arrangements [13].
• ASFV markedly slowed transport of cathepsin D to lysosomes, demonstrating that loss of TGN structure correlated with loss of TGN function [14].
• Cathepsin D from pig myometrium. Characterization of the proteinase [15].
• The purification of cathepsin D from pig uterus by two-step affinity chromatography on concanavalin A- and pepstatin-Sepharose was described previously [Afting & Becker (1981) Biochem. J. 197, 519-522] [15].

Associations of CTSD with chemical compounds

• The disulfide bond arrangement in cathepsin D is probably similar to that of pepsin, because the positions of six half-cystine residues are conserved [8].
• These properties are very similar to those of pseudorenin, an angiotensin-forming enzyme originally isolated from human kidney, indicating that cathepsin D and pseudorenin may be identical [9].
• Thus, the membrane-translocated molecule was apparently a high mannose glycoprotein from which a signal peptide had been cleaved, as observed for the lysosomal protease cathepsin D (Erickson, A. H., and Blobel, G. (1979) J. Biol. Chem. 254, 11771-11774) [16].
• Thyroglobulin type-1 domains in equistatin inhibit both papain-like cysteine proteinases and cathepsin D [17].
• Biosynthesis of a lysosomal enzyme. Partial structure of two transient and functionally distinct NH2-terminal sequences in cathepsin D [18].

Other interactions of CTSD

• Antibodies directed against the epithelial plasma membrane protein E-cadherin, the lysosomal membrane protein LAMP-1, and the lysosomal matrix protease cathepsin-D were used [19].
• When the sequence of cathepsin D, renin, and pepsin are aligned, 32.7% of the residues are identical [8].
• Remarkably, equistatin also strongly inhibits cathepsin D with Ki = 0.3 nM but not other aspartic proteinases such as pepsin, chymosin, and HIV-PR [17].
• The action of uterine cathepsin D on the insulin A-chain (S-sulfo) and porcine glucagon was compared with the action of bovine dental pulp cathepsin on the same substrates [20].
• It did not inhibit cathepsin D, carboxypeptidase A, pancreatic kallikrein or trypsin [21].

Analytical, diagnostic and therapeutic context of CTSD

• Various biosynthetic forms of porcine spleen cathepsin D (Erickson, A. H. and Blobel, G. (1979) J. Biol. Chem. 254, 11771-11774), isolated by immunoprecipitation of in vivo- and in vitro-synthesized products, have been characterized by partial NH2-terminal sequence analysis [18].
• Cathepsin D was purified by two-step affinity chromatography on concanavalin A-- and pepstatin--Sepharose [22].
• The substrate specificity of porcine pepsin has been altered by site-directed mutagenesis in an attempt to selectively cleave bovine hide collagen at only a few sites, similar to cathepsin D, for the production of high quality gelatin [23].
• For the differential diagnosis between vital and postmortem wounds, our results showed that the most useful markers studied are the Cathepsin A and D activities, Cathepsin D that of the first one [24].
• Net production of ET-1 reached a maximum when 0.003 U of cathepsin D was used, and about 16% of the initial proET-1 was detected as ET-1 by HPLC [25].

References