Disease relevance of CPD

• In contrast to the restricted expression in the normal adenohypophysis, CPD appeared to be widespread in the majority of adenomas, suggesting that CPD levels are increased in adenomas [1].
• This study evaluated the expression patterns of CPE, CPD, and CPZ immunoreactivity in 48 pituitary adenomas [1].
• Luciferase reporter assays with various size constructs containing the promoter region upstream of the start sites showed that it was active in three different cell lines, especially in the human hepatoma cell line HepG2 and the human monocytic cell line THP-1, which have high constitutive expression of CPD [2].
• The sequence is similar (75% identity) to duck gp180, a protein that was isolated, cloned and sequenced as a hepatitis B virus-binding protein but not characterized as a carboxypeptidase [3].
• Apparent toxicity thresholds were associated with large increases in steady-state CPD levels [4].

Psychiatry related information on CPD

• The utility of CPD for older adult mental health nurses [5].

High impact information on CPD

• Substrate specificity is altered by DNA damage, such that AfXPB unwinds dsDNA with 3' extensions, but not blunt-ended dsDNA, unless it contains a lesion, as shown for CPD or (6-4) photoproducts [6].
• The CD8+CD28- subset of IEC-activated CD8+ T cells, which express CD101 and CD103, interacts with IECs through gp180 and has regulatory function [7].
• In contrast, gp-180-deficient neutrophils interacted in a normal fashion with endothelial monolayers, attaching to their surfaces and migrating between cell junctions to spread between the monolayers and the subjacent plastic [8].
• Compared with normal neutrophils. gp-180-deficient neutrophils showed decreased adhesion to cold-insoluble globulin-coated plastic surfaces, and their ability to spread on this substratum was greatly impaired [8].
• We conclude that the abnormal function of gp-180-deficient cells is unlikely to be caused by a faulty interaction with the vascular endothelium [8].

Chemical compound and disease context of CPD

• Blood was collected into CPD or heparin immediately before and 15 min after an intravenous dose of 0.2 micrograms/kg body weight of DDAVP [9].
• In addition, dietary supplements of anti-oxidant, alpha-tocopherol, fed to LBAM larvae were successful in reducing the toxicity of CPD [10].
• For the purpose of understanding better the mode of action of alkanes on insects, the relationship between mortality, weight loss in oxygen enriched atmospheres and dietary antioxidants was examined using an alkane, C15 Ampol CPD and a spray oil, C23 DC-Tron NR, on lightbrown apple moth, Epiphyas postvittana Walker, (LBAM) [10].
• We show here that gE/gI and a second glycoprotein, gB, TGN46, and another cellular protein, carboxypeptidase D, all moved to cell junctions after infection with an HSV mutant unable to produce cytoplasmic capsids [11].

Biological context of CPD

• Human carboxypeptidase D (CPD) is a 180-kDa type I membrane protein with three tandem active site domains [2].
• Multiple transcription start sites were found in the CPD gene within a GC-rich sequence lacking the typical TATA box, but containing three GC boxes [2].
• The human carboxypeptidase D (CPD) gene was found to encompass approximately 88.3 kb of genomic sequence, containing 21 exons ranging in size from 65 to 1813 bp, and 21 introns ranging in size from 112 bp to 35.6 kb [2].
• The NO synthase inhibitor N-monomethyl-L-arginine blocked the inhibitory Arg effect and the NO donor S-nitroso-acetylpenicillamine mimicked it, indicating that high levels of NO block the up-regulation of CPD [12].
• RESULTS: CPD 5-induced EGFR phosphorylation was functional to stimulate Ras pathway [13].

Anatomical context of CPD

• Immunostaining localized CPD primarily in a perinuclear/Golgi region, whereas CPM was on the cell membrane [14].
• The present work provides evidence for the co-localization of CPE and CPD to basal plate extravillous trophoblasts and maternal uteroplacental vascular endothelial cells, chorionic villous endothelial cells, amnionic epithelial cells, and umbilical venous and arterial smooth muscle cells [15].
• Carboxypeptidase D (CPD), a carboxypeptidase with CPE-like activity, is widely distributed in tissues and is present in the trans-Golgi network [15].
• Whereas the intensity of CPD immunostaining is similar in the placenta and umbilical cord, CPE staining in the placenta is much weaker than in the umbilical cord, suggesting that CPD plays a more important role in the processing of placental peptides [15].
• The antiserum to the full length CPD is internalized to a structure that co-stains with furin and wheat germ agglutinin, but is distinct from transferrin recycling endosomes [16].

Associations of CPD with chemical compounds

• CPD is a B-type (or kininase I-type) carboxypeptidase that cleaves C-terminal basic residues from proteins and peptides, such as Arg9 from bradykinin [2].
• Some of the constructs contained the three Cys residues present in the CPD transmembrane region, while other constructs contained Ala in place of the Cys [17].
• Thus, the covalent attachment of palmitic acid to the Cys residues of CPD has a functional significance in the trafficking of the protein [17].
• A construct containing the Cys residues of the CPD transmembrane domain was soluble in Triton X-100 as was endogenous palmitoylated CPD, indicating that palmitoylation does not target CPD to detergent-resistant membrane rafts [17].
• The internalization of CPD is not substantially affected by treatment of the AtT-20 cells with brefeldin A [16].

Regulatory relationships of CPD

• PRL/E2-induced cell-surface CPD released Arg from extracellular substrates, increased intracellular NO, promoted survival and inhibited apoptosis of MCF-7 cells [18].

Other interactions of CPD

• Aplysia CPE and the CPD-related enzyme are candidate processing enzymes that may play a role in the processing of the ELH prohormone and other Aplysia prohormones [19].
• A novel neuronal Aplysia enzyme was also identified by the polymerase chain reaction that was most closely related to the carboxypeptidase D (CPD)-related duck protein gp180 and the Drosophila silver gene carboxypeptidases [19].
• Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the active 50-kilodalton subunit of human carboxypeptidase N (CPN1) [20].
• We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes [21].
• Highly selective expression of CPD in corticotrophs suggests that CPD plays a particularly important role in prohormone (POMC) processing in corticotrophs, with minimal or no significant roles in non-corticotrophs [22].

Analytical, diagnostic and therapeutic context of CPD

• RAW 264.7 cells contained significant membrane-bound CPD activity as shown by activity assays and immunoprecipitation [12].
• Northern blotting of mRNA from human tissues and cells showed high levels of CPD mRNA in placenta, pancreas and Hep G2 hepatoma cells, and smaller amounts in skeletal muscle, heart and HT-29 colon carcinoma and melanoma cell lines [3].
• By immunohistochemistry, ACTH-IR cells within CSCI and basophil invasion showed uniformly weak reactivity and common patterns for cytokeratins (CAM5.2 and 35 beta H11), carboxypeptidase D, and LeuM1, whereas those outside CSCI showed a great variety of immunoreactivity [23].
• Human neutrophils were stored in vitro in CPD or CPD-adenine plasma under conditions designed to simulate those of leukapheresis followed by short-term preservation [24].
• Labor records were reviewed for BW and complications, defined as: instrumental delivery, cesarean section (C/S) for nonprogress of labor or "CPD," and "difficult" vaginal delivery [25].

References