Disease relevance of Anpep

• Rat aminopeptidase M shows 77% similarity with the recently cloned human enzyme, as well as weaker but significant similarity with aminopeptidase N from E. coli (18%) and with human leukotriene A4 hydrolase (21%) [1].
• beta-Aminopropionitrile (beta APN), 500 ng/g body weight was injected intraperitoneally into male rats every 2 days between 2 and 28 days after birth [2].
• The results suggest that beta APN administered topically in an appropriate vehicle penetrates the granuloma tissue and affects collagen polymerization [3].
• Because acute experimental autoimmune encephalomyelitis (EAE) is characterized by a transient and focal perturbation of the BBB, we have utilized the model of adoptive transfer EAE to correlate the expression of the pericytic aminopeptidase N (pAP N) with the acute functional state of the BBB [4].
• In this way, APN could represent a new therapeutic target in pathological processes, such as tumoral proliferation and/or angiogenesis associated with cancer development, where an increase in the level of this enzyme has been observed [5].

Psychiatry related information on Anpep

• Thus, the activity of aminopeptidase N in the hippocampus and soluble puromycin-sensitive aminopeptidase in the frontal cortex were found to be lower in rats experiencing naloxone precipitated withdrawal symptoms, compared to the corresponding controls [6].
• Chronic APM ingestion failed to influence diurnal feeding patterns, meal size distributions, or diurnal patterns of spontaneous motor activity [7].

High impact information on Anpep

• Angiotensin I, II, and III; angiotensin-converting enzyme; aminopeptidase A and aminopeptidase n; at(1); and at(2) receptors were shown to be present in the internal anal sphincter [8].
• Expression of 2 markers of enterocyte differentiation, aminopeptidase N and villin, was induced in IEC-6/Cdx1 cells [9].
• Colocalization at the electron microscopic level showed that the apical protein, dipeptidyl peptidase IV, was in the same structures as aminopeptidase N, polymeric IgA receptor, or intravenously injected horseradish peroxidase [10].
• APM was detected in the brush border of the epithelium of the proximal convoluted tubule of the kidney and of the small intestine, and it was localized to cells scattered throughout lymphoid tissue in the small intestine and colon [11].
• The major immunoreactive protein identified in membranes prepared from all tissues had an apparent molecular weight of 140, corresponding to the monomer of APM [11].

Chemical compound and disease context of Anpep

• DMSO significantly enhanced the effect of beta APN in reducing the cross-linking of collagen. beta APN administered onto urea-pretreated skin and followed by occlusion in the granuloma tissue was more effective than beta APN in 30% DMSO, but only in the parameter reflecting extractibility of collagen into urea or thiocyanate solutions [3].
• Pre-incubation of rat PTCs with either acivicin, an inhibitor of gamma-glutamyl transpeptidase (gamma-GT), or bestatin, an inhibitor of aminopeptidase M, resulted in increased toxicity of 5-(glutathion- S-yl)-alpha-MeDA but had no effect on 2,5- bis(glutathion- S-yl)-alpha-MeDA-mediated cytotoxicity [12].
• In the present study we describe changes in aorta at the protein level associated with allylamine (AA) and beta-aminopropionitrile (beta APN) induced vascular toxicity in a rat model [13].
• We conclude that topically administered beta APN fumarate onto the intact skin penetrates the stratum corneum and effectively inhibits collagen crosslinking in the underlying granuloma tissue [14].
• Administration of beta-aminopropionitrile (beta APN) fumarate on the intact skin overlying the implanted PVA sponge in the presence and absence of dimethyl sulfoxide (DMSO) during the growth phase of granuloma development (4th through 12th days after implantation) was accompanied by significant inhibition of collagen polymerization [14].

Biological context of Anpep

• Amino acid sequence deduced from a rat kidney cDNA suggests it encodes the Zn-peptidase aminopeptidase N [15].
• Taken together with the observation that only a single gene homologous to KZP DNA is present in the rat and human genomes, these results suggest that we have established the primary structure of rat kidney aminopeptidase N [15].
• In addition, the rat aminopeptidase M sequence contains an eight amino acid consensus sequence believed to serve as the zinc binding domain in a family of zinc-metallohydrolases [1].
• The major APN transcript of the alveolar type II epithelial cell originates from a unique upstream promoter region [16].
• Hydrolysis of the substrates was shown to be a two-step process involving initial cleavage by endopeptidase with secondary hydrolysis of the peptide products by brush-border membrane aminopeptidase N. Hydrolysis of both substrates was maximum at a neutral pH and was strongly inhibited by metal chelating agents, phosphoramidone, and amastatin [17].

Anatomical context of Anpep

• Brain microvessels and intestine brush-border cells were shown to present a high concentration of aminopeptidase N. Moreover, a labeling of various brain structures was observed [18].
• Aminopeptidase N was also visualized in moderate to high levels in other brain structures such as the hippocampus, nucleus accumbens, substantia nigra, hypothalamus (dorsomedial and ventromedial nuclei), raphe nucleus, pontine nucleus, inferior olive, and in high concentration in the granular layer of cerebellum [18].
• First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129 [18].
• APM was localized to numerous fibers supplying the myenteric plexus of the stomach, small intestine, and colon [11].
• APM was characterized in membranes prepared from the muscle and mucosa of the guinea pig and rat stomach, small intestine, and colon by Western blotting [11].

Associations of Anpep with chemical compounds

• Aminopeptidase N, which preferably removes NH2-terminal neutral amino acids from peptides, has probably a host of substrates [18].
• Treatment of hepatocytes or WIF-B cells with phosphoinositide 3-kinase inhibitors, wortmannin or LY294002, led to accumulation of the apical plasma membrane proteins, 5'-nucleotidase and aminopeptidase N in lysosomal vacuoles [19].
• The method is based on the sequential cleavage of the synthetic peptide substrate, glutaryl-alanyl-alanyl-phenylanyl-4-methoxy-2-naphthylamide, by NEP and exogenous aminopeptidase M to yield free 4-methoxy-2-naphthylamine (MNA) [20].
• beta-Aminopropionitrile (beta APN) was administered intraperitoneally to rats on postnatal days 1, 3, and 5 [21].
• We demonstrate here that gp160 has structural homology to aminopeptidase N and possesses aminopeptidase activity in vitro [22].

Physical interactions of Anpep

• Enkephalinase was localized by using a coupled enzyme assay based upon the sequential cleavage of the synthetic peptide substrate glutaryl-ala-ala-phe-4-methoxy-2-naphthylamide by enkephalinase and exogenous aminopeptidase M. Enzyme distribution was examined in segments from cervical, thoracic, lumbar, and sacral cord [23].
• Approximately 60% of the dipeptidyl peptidase IV interacted with either one or both of the lectins while only 30% of the aminopeptidase N did so [24].

Other interactions of Anpep

• This co-localization confirms the physiological implication of aminopeptidase N in the inactivation of enkephalins accounting for the requirement of dual inhibition of neutral endopeptidase and aminopeptidase N to observe highly significant morphine-like effects induced by the protected endogenous opioid peptides [18].
• Our results suggest that both apical (HA 4, dipeptidylpeptidase IV, and aminopeptidase N) and basolateral (CE 9 and the asialoglycoprotein receptor [ASGP-R]) proteins reach the hepatocyte plasma membrane with similar kinetics [25].
• Compared with homogenates, the membranes were enriched 55- to 56-fold in gamma-glutamyltransferase, aminopeptidase M, and alkaline phosphatase activities and showed very low enrichment in markers of other membranes [26].
• S-(1,2-Dichlorovinyl)-L-cysteinylglycine, a putative metabolite of DCVG, also produced cell death, which was prevented by 1,10-phenanthroline, phenylalanylglycine, and aminooxyacetic acid, inhibitors of aminopeptidase M, cysteinylglycine dipeptidase, and cysteine conjugate beta-lyase, respectively [27].
• Neomucosal lactase, sucrase, aminopeptidase N, and alkaline phosphatase activity was determined by incubation with enzyme specific substrate [28].

Analytical, diagnostic and therapeutic context of Anpep

• Molecular cloning and amino acid sequence of rat kidney aminopeptidase M: a member of a super family of zinc-metallohydrolases [1].
• Aminopeptidase M (APM) was localized in the kidney and alimentary tract of guinea pigs and rats by indirect immunohistochemistry [11].
• Immunoprecipitation of high salt extracts of cultured VSMC with ASMM and APM yields myosins with the same mobilities on SDS PAGE [29].
• These hypotheses were supported by site-directed mutagenesis; the mutants lost omegapeptidase but displayed alanyl-aminopeptidase activity [30].
• Regulation of a blood-brain barrier-specific enzyme expressed by cerebral pericytes (pericytic aminopeptidase N/pAPN) under cell culture conditions [31].

References