Disease relevance of DPEP1

• Using immunobead RT-PCR, a technique that first enriches for epithelial cells, we found DPEP1 positive cells in intra-peritoneal lavage and venous blood samples from 15/38 (39%) colorectal cancer cases [1].
• However, 18FDG detected fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of patients with osteoblastic disease (P < .05) [2].
• We have compared 18FDG PET with 99mTc MDP bone scintigraphy in patients with skeletal metastases from breast cancer and have analyzed the data in subgroups based on radiographic characteristics of lesions [2].
• In contrast all stable transformed cell lines that were tested, derived either by transformation with the DNA tumour viruses SV40 or adenovirus, or in human tumour cell lines, contained very low levels of or no detectable MDP mRNA or enzyme activity [3].
• Thus, MDP-stimulated bone resorption in vitro is mediated by a mechanism which is not dependent upon prostaglandins or osteoclast-activating factor [4].

Psychiatry related information on DPEP1

• 48 patients with episodic psychosis (18 schizophrenia, 30 MDP) were studied to examine whether they had similar hallucinations in consecutive episodes [5].
• We randomly selected 35 PD patients, 33 MDP patients, 27 MD patients and 30 normal volunteers with no family history of anxiety or mood disorder [6].
• A total of 16 (45.7%) PD patients, 12 (36.4%) MDP patients, four (11.1%) MD patients, and two (6.7%) normal volunteers had a panic attack after hyperventilating [6].
• Recent observations argue in favor of the presence of an MDP bacterial structure in mammalian mediators which increase slow-wave sleep and/or produce fever [7].
• Treatment of cultured monocytes with the synthetic adjuvants N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and its lipophilic derivative, [B30]-MDP, did not significantly affect the D2V permissiveness of the cells [8].

High impact information on DPEP1

• Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MPhi/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MPhis and DCs [9].
• In this issue of Neuron, de Carvalho Aguiar and colleagues report the identification of missense mutations in the gene for the Na+/K+ -ATPase alpha3 subunit (ATP1A3) as a cause of rapid-onset dystonia-parkinsonism (RDP, DYT12) [10].
• RESULTS: 18FDG PET detected more lesions than 99mTc MDP scintigraphy (mean, 14.1 and 7.8 lesions, respectively; P < .01) [2].
• Expression of immunologically cross-reactive and enzymatically active MDP was attained in COS cells transfected with the cDNA [11].
• Carbohydrate analyses of the purified human dipeptidase demonstrated that it was not a glycoprotein, a characteristic that distinguishes it from porcine and rat renal dipeptidase. beta-Lactamase activity of the purified human enzyme was demonstrated by measuring its activity against the two beta-lactam antibiotics, imipenem and SCH 29482 [12].

Chemical compound and disease context of DPEP1

• PURPOSE: 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is currently the method of choice for the detection of bone metastases, but 18F-fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior spatial resolution and improved sensitivity [2].
• Clinical evaluation of the immunoadjuvant murabutide, a derivative of MDP, administered with a tetanus toxoid vaccine [13].
• This study investigated the effects of hyperthermia and a surrogate of infection (muramyl dipeptide or MDP) on cytokine production and mortality in a neonatal rat model [14].
• Uptake of technetium 99m MDP by hepatoblastoma [15].
• Twenty-one hospitalized patients with infectious diseases were randomly assigned to receive either thienamycin formamidine/renal dipeptidase inhibitor or cefazolin [16].

Biological context of DPEP1

• Using somatic cell hybrids carrying either different human chromosomes or chromosome 16 segments, we confirm and refine the physical mapping of DPEP1 to the chromosome 16 subregion q24 [17].
• Using the VNTR polymorphism, DPEP1 was shown to be linked to D16S7 with a maximum lod score of 5.8 at a recombination fraction of 0.03 [17].
• DPEP1 is implicated in the renal metabolism of glutathione and its conjugates and is also responsible for hydrolysis of beta-lactam antibiotics [18].
• Assignment of the human renal dipeptidase gene (DPEP1) to band q24 of chromosome 16 [18].
• The N-terminal sequence of human renal dipeptidase showed a high degree of similarity with that of the pig enzyme, and enzymic deglycosylation revealed that the difference in size of renal dipeptidase between these two species is due almost entirely to differences in the extent of N-linked glycosylation [19].

Anatomical context of DPEP1

• Using cDNA micro-array screening, we found dipeptidase 1 (DPEP1) to be highly expressed in colon tumors compared to matched normal mucosa [1].
• Renal dipeptidase (EC 3.4.13.11) has been purified from human kidney cortex by affinity chromatography on cilastatin-Sepharose following solubilization with either n-octyl-beta-D-glucopyranoside or bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) [19].
• Membrane dipeptidase (MDP) is a zinc metalloenzyme located in the lungs and on the brush border membranes of the kidney and intestine [3].
• In BRK cells transformed by the temperature-sensitive tsA58 mutant of SV40 T antigen, MDP activity was not detectable, in cell lines grown at the permissive temperature (33 degrees C) but after 5-14 days of incubation at the non-permissive temperature (39.5 degrees C), MDP protein and enzyme activity could be readily detected [3].
• It was finally revealed that the migration of monocytes was enhanced by MDP [20].

Associations of DPEP1 with chemical compounds

• Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics [21].
• We also examined the substrate specificity of human MDP and found that human MDP catalyzed the hydrolysis of S(substituent)-L-cysteinyl-glycine adducts such as L-cystinyl-bis(glycine) and S-N-ethylmaleimide-L-cysteinyl-glycine, as well as the conversion of leukotriene D4 to leukotriene E4 [22].
• The purified human MDP was found to be homogeneous on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis [22].
• Native collagen (type II) from human costal cartilage was emulsified with incomplete Freund's adjuvant (IFA) containing the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and injected into one hind footpad of the PVG/c rat [23].
• The binding of the synthetic immunoadjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP, for muramyl dipeptide) to human and rabbit sera containing peptidoglycan (PG) antibodies was investigated [24].

Other interactions of DPEP1

• For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1 [25].

Analytical, diagnostic and therapeutic context of DPEP1

• Primary structure of human microsomal dipeptidase deduced from molecular cloning [11].
• Northern blotting hybridization analysis showed that renal dipeptidase mRNA is only transcribed in kidney [26].
• After treatment with endoglycosidase F, human MDP showed a single band with an apparent Mr of 42 kDa on SDS-polyacrylamide gel electrophoresis [22].
• These studies indicate that the radioimmunoassays employed basically are applicable for the selection of nonimmumogenic MDP analogs possessing immunoadjuvant activity [24].
• Several methods of measuring free (99m)Tc-MDP have been described including ultrafiltration, precipitation using trichloroacetic acid, and a direct in vivo measurement based on the assumption that free MDP is cleared through the kidneys by glomerular filtration [27].

References