Disease relevance of PGPEP1

• In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls [1].
• Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer [2].
• Investigations on enzymatic properties showed that the Pcp over-expressed in E. coli disclosed properties similar to those found for the enzyme extracted from S. pyogenes or for some other Pcps studied previously [3].
• Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression [4].
• CONCLUSIONS: PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian duct and its derivations; postnatally, it is restricted to a few cells derived from the initial and terminal segment of the Wolffian duct, and to neuroendocrine cells in prostate cancer specimens [5].

High impact information on PGPEP1

• Autonomic fibres in the mucosa were stained with a neurone-specific polyclonal antibody, PGP 9 [6].
• However, unlike what is seen in planta, some additional transport of the benzoic acid is observed in yeast and mammalian cells expressing AtPGP1, suggesting that other factors present in plant tissues confer enhanced auxin specificity to PGP-mediated transport [7].
• The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold) [2].
• Tannic acid decreased calcein efflux and the expression of PGP, MRP1 and MRP2 membrane efflux pumps [8].
• PGP was phosphorylated in membrane vesicle preparations in vitro only when coexpressed with PKC alpha, and phosphorylation was Ca(2+)-dependent and inhibited by the PKC inhibitor Ro 31-8220 [9].

Chemical compound and disease context of PGPEP1

• Benarthin, a new inhibitor of pyroglutamyl peptidase (PG-peptidase), has been isolated from the culture filtrate of Streptomyces xanthophaeus MJ244-SF1 [10].

Biological context of PGPEP1

• As an impaired enzyme function caused by genetic alterations might increase the amount of immunogenic gluten peptides, we conducted a comprehensive functional genomics analysis of PGPEP1, including DNA sequencing, genetic association testing, and quantifying RNA expression [11].
• We describe the cloning and sequencing of the human (AJ278828) and mouse (AJ278829) forms of pyroglutamyl-peptidase I. The deduced amino acid sequences each consist of 209 residues and show approximately 30% identity with bacterial forms of the enzyme [12].
• Wash-out kinetics of 99mTc-MIBI and the scintigraphic determination of PGP expression [13].
• Pyrrolidone carboxyl peptidase (EC 3.4.11.8) (Pcp), an enzyme which selectively removes pyrrolidone carboxylic acid (PCA) from some PCA-peptides and -proteins, was demonstrated in bacteria and in plant, animal and human tissues [3].
• To study the possible involvement of TRH neurons in learning and memory processes, gene expression of TRH, its receptors, and pyroglutamyl peptidase (PPII), were measured in limbic regions of water-maze trained rats [14].

Anatomical context of PGPEP1

• Pyroglutamyl peptidase I and prolyl endopeptidase in human semen: increased activity in necrozoospermia [15].
• In the ejaculatory ducts, the PGP 9.5-immunoreactive cells were free of immunoreactivity for semenogelin, the major secretory product of the ejaculatory-vesicular-ampullary complex, and they also lacked chromogranin A-immunoreactivity [5].
• Moreover, fluoxetine (10 micro M) induces approximately 30% inhibition of PGP activity in Caco-2 cells [16].
• Nerve fibers were revealed using immunoperoxidase staining with panaxonal antibody PGP 9 [17].
• Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis [18].

Associations of PGPEP1 with chemical compounds

• Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1 [7].
• Proteins with N-terminal pyroglutamic acid were enzymatically deblocked by in situ pyroglutamyl peptidase digestion, and N-acetylated proteins were also enzymatically deblocked with acylamino acid-releasing enzyme (AARE) after on-membrane digestion with trypsin to generate the N-terminal peptide fragment [19].
• In contrast, PGP ATPase activity was increased by PKC alpha as well as by verapamil, but only PKC-stimulated activity in the presence of verapamil was inhibited by Ro 31-8220 [9].
• We have developed two new prodrugs, 4-[N,N-bis(2-chloroethyl)amino]-phenoxycarbonyl-L- glutamic acid (PGP) and (S)-2-[N-[4-[N,N-bis(2-chloroethyl)amino]- phenoxycarbonyl]amino]-4-(5-tetrazoyl)butyric acid (PTP), which are cleaved by the bacterial enzyme CPG2 to release the 4-[N,N-bis(2-chloroethyl)amino] phenol drug [20].
• As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium [21].

Physical interactions of PGPEP1

• TPA treatment did not affect the activity of the cytosolic enzyme pyroglutamyl peptidase I (EC 3.4.19.3) or the membrane-bound enzyme dipeptidyl peptidase IV (EC 3.4.19.3) [22].

Other interactions of PGPEP1

• 1. The following proteolytic enzymes were measured in muscles of control subjects and patients with muscular dystrophies and related neuromuscular diseases: an elastase-like enzyme, carboxypeptidase A, carboxypeptidase B and pyroglutamyl peptidase [23].

Analytical, diagnostic and therapeutic context of PGPEP1

• Through the use of molecular modeling techniques, peptide analogs of the CDR3-like region of the human CD4 molecule, analog hPGP, a cyclized peptide 13 amino acids long, was synthesized and tested for its ability to inhibit proliferation in human mixed lymphocyte reactions [24].
• Frozen sections were stained with specific antibodies to GAP-43 and protein gene product 9.5 (PGP, a general neuronal marker) [25].
• Twenty-two hemangiomas and arteriovenous malformations were studied using indirect immunocytochemistry with antibodies against the nerve markers protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP) [26].
• Pyroglutamyl peptidase was partially purified from Enterococcus faecalis ATCC 19433 by anion-exchange chromatography, gel filtration and salting out after lysis of cell walls with N-acetylmuramidase [27].
• A possible explanation is mentioned in the literature by an increase in PGP level and multi-drug resistance, so we suggest that it may play a role in impaired Tc-99m MIBI uptake in the thyroid phase and recommend cessation of vitamin D3 metabolites before performing parathyroid scintigraphy [28].

References