Disease relevance of Prep

• To study the function of these domains, we deleted different portions of the PE structural gene and expressed these constructs in E. coli using an inducible T7 promoter [1].
• PERA/Ei (PE) mice are highly susceptible to tumor induction by polyoma virus, whereas C57BR/cdj (BR) mice are highly resistant [2].
• A PE protein expressed by Mycobacterium avium is an effective T-cell immunogen [3].
• Pre-eclampsia (PE) is the most severe pregnancy-related disease, leading to high maternal and fetal morbidity/mortality [4].
• Mouse Neuro-2a neuroblastoma and rat C6 glioma cloned cells were screened for neuropeptide-metabolizing peptidases using a kininase bioassay combined with a time-course bradykinin-product analysis, and a fluorimetric assay for prolyl endopeptidase [5].

Psychiatry related information on Prep

• Its action on vasopressin has been proposed as the underlying mechanism accounting for the ability of inhibitors of prolyl oligopeptidase to reverse scopolamine-induced amnesia in rats [6].
• Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD) [7].

High impact information on Prep

• Inhibitors of prolyl oligopeptidase reverse the effects of all three drugs on sensory neuron growth cone area and collapse [8].
• Moreover, the development of Dictyostelium is sensitive to lithium and to valproic acid, but resistance to both is conferred by deletion of the gene that codes for prolyl oligopeptidase, which also regulates inositol metabolism [8].
• Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop [9].
• We found a highly conserved Phox2b proximal enhancer that mediates rhombomere-restricted expression and contains separate Pbx-Hox (PH) and Prep/Meis (P/M) binding sites [10].
• PE mice respond to viral infection with a type 2 (IL-10) and BR mice with a type 1 (IL-12) cytokine response, underlining the importance of a sustained T cell response for effective antitumor immunity [2].

Chemical compound and disease context of Prep

• F9 teratocarcinoma cells, when grown in suspension in the presence of retinoic acid (RA), differentiate into embryoid bodies (EBs) which can be used as a model system to study the spatially appropriate induction of VE- and PE-specific gene expression [11].
• Poststatin, a new inhibitor of prolyl endopeptidase (PEP) was discovered in the fermentation broth of Streptomyces viridochromogenes MH534-30F3 [12].

Biological context of Prep

• We have cloned and characterized the genomic structure of the mouse gene for prolyl oligopeptidase that is mapped to chromosome 10B2-B3 [13].
• Comparison with the presumed domain structures of the mouse prolyl oligopeptidase indicates that the propeller domain of the enzyme is encoded by exons 3-10, whereas the catalytic domain is encoded by exons 1-3 and 10-15 [13].
• Murine T cells expressing high activity of prolyl endopeptidase are susceptible to activation-induced cell death [14].
• A cDNA for mouse prolyl endopeptidase (PEP) was cloned and its nucleotide sequence determined [15].
• In the enhancer, an Oct-1 binding site, a Pbx/Prep binding site, Msx/Dlx binding sites, and a previously unidentified protein-binding element at -1793, all contribute to TPA suppression [16].

Anatomical context of Prep

• Representative aminopeptidases and prolyl endopeptidase from murine macrophages: comparative activity levels in resident and elicited cells [17].
• cDNA cloning of mouse prolyl endopeptidase and its involvement in DNA synthesis by Swiss 3T3 cells [15].
• Sperm Prep column washes were toxic to mouse gametes and embryos and human sperm and had gel formation with the Limulus Amoebocyte Lysate assay [18].
• When broth cultures enter the post-exponential growth (PE) phase or experience amino acid limitation, L. pneumophila accumulates the stringent response signal (p)ppGpp and expresses traits likely to promote transmission to a new phagocyte [19].
• When administered intraperitoneally to mice, Fmoc-alanyl-pyrrolidine-2-nitrile crosses the blood-brain barrier to inhibit brain prolyl oligopeptidase [6].

Associations of Prep with chemical compounds

• The activity of prolyl endopeptidase in the cell lysate was also dose-dependently decreased by the addition of glutathione disulfide and the decrease of the activity was prevented by coexistence of reduced glutathione [20].
• Kininase and prolyl endopeptidase activities in C6 cells were recovered mostly in the soluble fraction [5].
• Since prolyl endopeptidase readily degrades many proline-containing neuropeptides, the inhibitor should be of value in studies on the role of the enzyme in neuropeptide metabolism [21].
• Prolyl endopeptidase: inhibition in vivo by N-benzyloxycarbonyl-prolyl-prolinal [21].
• (Benzyloxycarbonyl)glycylprolylmelphalan, but not the more sterically hindered doxorubicin prodrug, could be efficiently activated by prolyl endopeptidase [specific activity = 813.3 nmol min(-1) (mg of enzyme)(-1) at 25 degrees C] [22].

Enzymatic interactions of Prep

• The culture supernatant was concentrated using a stirred cell with a 50 kDa cut-off membrane at 40 degrees . Further purification was carried out using Prep cell [23].

Regulatory relationships of Prep

• Specific inhibitor for prolyl endopeptidase suppresses the generation of amyloid beta protein in NG108-15 cells [24].
• In ovariectomized mice, prolyl endopeptidase activity was significantly higher in the uterus treated with progesterone or estradiol than in the uterus treated with vehicle oil only or a dopamine antagonist (perphenazine) which stimulates prolactin secretion [25].

Other interactions of Prep

• The specific activity measured on Arg-Arg-2-NNap for DPP III and the hydrolysis of Boc-Arg-Pro-2-NNap for prolyl endopeptidase were higher in the Emory Mouse cataractous lens extract [26].
• Prevention of amyloid-like deposition by a selective prolyl endopeptidase inhibitor, Y-29794, in senescence-accelerated mouse [27].
• Specific inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase do not change the in vitro release of TRH or its content in rodent brain [28].
• Several enzymatic activities, including those of angiotensin-converting enzyme, esterase, trypsin-like enzyme, post-proline-cleaving enzyme, and Gly-Pro-aminopeptidase, showed rhythmic oscillations with about one cycle per 3 months throughout the period of 30 months [29].
• Protease activities with specificity toward synthetic substrates, Suc-Gly-Pro-Leu-Gly-Pro-MCA for prolyl endopeptidase or collagenase-like peptidase, and Suc-Ala-Ala-Pro-Phe-MCA for chymotrypsin were identified in the detergent-soluble fraction of herring spermatozoa [30].

Analytical, diagnostic and therapeutic context of Prep

• We have developed preparative in situ hybridization (Prep-ISH) of complex DNA populations to mitotic chromosomes as a means of generating chromosome region-specific DNA subpopulations [31].
• The activity of prolyl endopeptidase in homogenates of mouse tissues was determined 30 min after intraperitoneal injection of N-benzyloxycarbonyl-prolyl-prolinal (1.25 mg/kg), a potent transition state analog inhibitor (K1 = 14 nM) of prolyl endopeptidase (EC 3.4.21.26) [21].
• Valid and reliable animal models are urgently required to test this hypothesis and to better understand the mechanisms underlying PE [4].
• The present study showed that PE analgesia was increased by co-injection with protease inhibitors (bacitracin and bestatin) [32].
• Likewise, the reaction profile of Pep rIL-18 toward mAb was very similar to that of inactive but not active rIL-18 on sandwich ELISA [33].

References