Disease relevance of Anpep

• As a corollary, APN was expressed on monocyte, macrophage, and B lymphoma cell lines, but not on T hybridoma or thymoma cell lines [1].
• The Listeria peptide is digested by carboxypeptidase Y but resists aminopeptidase M, and only peptides with N-formyl methionine competitively block its presentation to CTL [2].
• Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer [3].
• Exon 1A-containing transcripts encoding p150 were expressed in all tissues examined from adult mice (brain, cecum, heart, kidney, liver, lung, spleen, and Peyer's patches) and were elevated most significantly in liver but remained lowest in brain following oral infection with Salmonella [4].
• APN was also expressed in colonic tumors, where it was present in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas examined [5].

High impact information on Anpep

• Ectopic expression of p150 in fibroblasts does not inhibit growth [6].
• T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides [7].
• Specific antibodies further identified the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing [7].
• A population of cells that express mast cell markers, including the membrane protein p161, but that lack expression of the high affinity IgE receptor, Fc epsilon RI, can be routinely grown from bone marrow [8].
• IgA and a brush border enzyme, aminopeptidase N, were colocalized in apical endosomes and small vesicles and were also frequently seen associated with the same vesicular profiles of glycolipid rafts [9].

Chemical compound and disease context of Anpep

• In contrast, APN was frequently localized at the luminal membrane of the surface epithelium in large-intestinal mucosa distal to tumors, adenomas and hyperplastic polyps, and from members of hereditary colon cancer syndrome families [5].
• The L-leucyl, L-valyl and L-isoleucyl derivatives were hydrolysed readily to MTX by aminopeptidase M (EC 3.4.11.2), while the L-pyroglutamyl and D-alanyl compounds were activated by pyroglutamate aminopeptidase (EC 3.4.19.3) (from Bacillus amyloliquefaciens) and D-aminopeptidase (from Ochrobactrum anthropi), respectively [10].
• We investigated the effect of bestatin, an inhibitor of aminopeptidase N (APN)/CD13 and aminopeptidase B, on the angiogenesis induced by B16-BL6 melanoma cells [11].
• Production of actinonin, an inhibitor of aminopeptidase M, by actinomycetes [12].
• Probestin, a new inhibitor of aminopeptidase M, produced by Streptomyces azureus MH663-2F6. I. Taxonomy, production, isolation, physico-chemical properties and biological activities [13].

Biological context of Anpep

• The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte differentiation antigen BP-1/6C3 suggested that it is a member of the zinc-dependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [microsomal aminopeptidase; alpha-aminoacyl-peptide hydrolase (microsomal), EC 3.4.11.2] [14].
• The position of the Thy-1 (theta cell surface antigen) locus on chromosome 9 of the mouse was determined relative to the biochemical markers Lap-1 (leucine arylaminopeptidase) and Mpi-1 (mannosephosphate isomerase) [15].
• This is corroborated by the fact that the selective APN inhibitor PC18 administered alone via the i.c.v. route increased arterial blood pressure [16].
• Backcross data produced the following gene order and map distances: Lap-1 (31.6 +/- 7.5 cM) Es-13 (2.6 +/- 2.6 cM) Mod-1 [17].
• Rab3 GAP consists of two subunits: the catalytic subunit p130 and the noncatalytic subunit p150 [18].

Anatomical context of Anpep

• Activity of APM and APA was found mostly in the fibrocytes which adhered to the basal membrane of the epithelium and glands [19].
• Histochemical study of aminopeptidase M, aminopeptidase A, and gamma-glutamyltransferase in the nasal cavity of laboratory rodents andman [19].
• p161, a murine membrane protein expressed on mast cells and some macrophages, is mouse CD13/aminopeptidase N [20].
• A mouse aminopeptidase N is a marker for antigen-presenting cells and appears to be co-expressed with major histocompatibility complex class II molecules [1].
• These antibodies were used to affinity purify functional mouse APN from both intestine and kidney, and by flow cytometry to examine the APN expression of the cells of the mouse immune system [1].

Associations of Anpep with chemical compounds

• This pressor response was blocked by prior treatment with the angiotensin type 1 receptor antagonist losartan, showing that blocking the action of APN on AngIII metabolism leads to an increase in endogenous AngIII levels, resulting in arterial blood pressure increase through an interaction with angiotensin type 1 receptors [16].
• These results demonstrate for the first time that (i) APA and APN are involved in vivo in the metabolism of brain Ang II and Ang III, respectively, and that (ii) the action of Ang II on vasopressin release depends upon the prior conversion of Ang II to Ang III [21].
• Mice received [3H]Ang II intracerebroventricularly (i.c.v.) in the presence or absence of the APN inhibitor, EC33 (3-amino-4-thio-butyl sulfonate) of the APN inhibitor, EC27 (2-amino-pentan-1,5-dithiol) [21].
• Recently, a potent APN inhibitor, PC18 (2-amino-4-methylsulfonyl butane thiol, methionine thiol), has been developed [22].
• This pressor response was blocked by prior treatment with the angiotensin type 1 (AT(1)) receptor antagonist, losartan, showing that blocking the action of APN on AngIII metabolism leads to an increase in endogenous AngIII levels, resulting in BP increase, through interaction with AT(1) receptors [23].

Regulatory relationships of Anpep

• Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain [24].

Other interactions of Anpep

• Secondly, we developed a specific and selective APA inhibitor, compound EC33 [(S)-3-amino-4-mercaptobutylsulphonic acid], as well as a potent and selective APN inhibitor, PC18 (2-amino-4-methylsulphonylbutane thiol) [16].
• By observing the segregation of alleles at the Mod-1 (cytoplasmic malic enzyme) locus, which is known to lie distal to these three markers, it was possible to show that Lap-1 is at the centromeric end of this gene group [15].
• Jejunal ApN and DPPIV activities were lower for obese mice before resection; ileal ApN activity was unaltered after resection for both strains [25].
• The results of our experiments show that in all brain parenchyma vessels of all sizes, pericytes and periendothelial cells are immunoreactive for aminopeptidase N, essentially at the plasma membrane level, and are also labeled by nestin specific antibodies, which decorate typical intermediate filaments [26].
• A small reduction in [Leu(5)]enkephalin degradation was detected in striatal membrane preparations of NEP-/- mice, if aminopeptidase N was additionally blocked by bestatin or amastatin [27].

Analytical, diagnostic and therapeutic context of Anpep

• A tyrosine residue was previously proposed to be involved in the enzymic activity of aminopeptidase N. Furthermore sequence alignment of mouse APA with other monozinc aminopeptidases indicates the presence of a conserved tyrosine (Tyr-471 in APA) [28].
• Immunocytochemistry experiments were carried out at the optical and electron-microscopic levels on mouse brain sections with antibodies specific for aminopeptidase N, aminopeptidase A, and the intermediate filament nestin [26].
• Inhibition of aminopeptidase N and neutral endopeptidase-24.11, two zinc metallopeptidases involved in the inactivation of the opioid peptides enkephalins, produces potent physiological analgesic responses, without major side-effects, in all animal models of pain in which morphine is active [29].
• By immunofluorescence studies using specific antibodies, aminopeptidase N appeared restricted to the apical microvillar domain, whereas the H2 histocompatibility antigen was distributed in the cytoplasm and lateral membranes [30].
• After treatment of this derivative with aminopeptidase M, the extent of inhibition correlated with the amount of MTX formed [10].

References