Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain

O'Leary, Rhona M.; Gallagher, Seán P.; O’Connor, Brendan

doi:10.1016/1357-2725(95)00154-9

Cited by 42 publications

(35 citation statements)

References 24 publications

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“…The presence of enzyme activity in both fractions is consistent with previous studies which have found that although PEP is predominately a cytosolic enzyme, activity associated with this enzyme is also present in membranes [O'Leary and O'Connor, 1995;O'Leary et al, 1996].…”

Section: Discussionsupporting

confidence: 80%

“…Although PEP has been described as a predominantly soluble cytosolic enzyme [Dresdner et al, 1982], it has become increasingly clear that PEP is found in both soluble and particulate forms. The latter is mainly localized in synaptosomal fractions, indicating that it may be involved in the degradation of peptides in the synaptic cleft [O'Leary and O'Connor, 1995;O'Leary et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

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Ontogeny of Soluble and Particulate Prolyl Endopeptidase Activity in Several Areas of the Rat Brain and in the Pituitary Gland

Agirregoitia

Irazusta²,

Ruíz³

et al. 2003

Dev Neurosci

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We have analyzed the activity of prolyl endopeptidase (PEP) in several areas of the rat brain (brain cortex, striatum, brain stem, cerebellum and hypothalamus) and in the pituitary gland during ontogeny. In all of these areas, we observed a reduction in PEP activity during development. However, the temporal profile of these alterations was found to be area specific and differences in the ontogeny of the soluble and particulate forms of PEP were observed. Thus, by postnatal day 20 (PD20), soluble PEP activity had began to decrease in the brain cortex and striatum, whereas decreased soluble PEP activity was observed earlier, at PD15, in the brain stem and cerebellum. Changes in the particulate fraction were even more pronounced. Senescence was associated with decreased soluble PEP activity in the striatum, but in contrast, particulate PEP activity was found to be increased in the senescent brain stem. The present results indicate that alterations in the levels of activity of PEP may represent an important event in the development and aging of the central nervous system.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Ontogeny of Soluble and Particulate Prolyl Endopeptidase Activity in Several Areas of the Rat Brain and in the Pituitary Gland

Agirregoitia

Irazusta²,

Ruíz³

et al. 2003

Dev Neurosci

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“…Here, we show that the PEP gene is primarily expressed in neurons but not in astrocytes. Because PEP exists both in cytosolic and membrane-bound forms (Dresdner et al, 1982;O'Leary et al, 1996;Irazusta et al, 2002), the finding that PEP expression is located in neurons strongly suggests that hydrolysis of neuropeptides catalyzed by PEP predominantly occurs on postsynaptic neurons, that also express neuropeptide receptors.…”

Section: Involvement Of Pep In Neuropeptide Catabolismmentioning

confidence: 94%

Localization of the mRNA encoding prolyl endopeptidase in the rat brain and pituitary

Bellemère

Vaudry

Mounien

et al. 2004

J of Comparative Neurology

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Prolyl endopeptidase (EC 3.4.21.26, PEP), a serine protease that hydrolyzes peptides at the carboxyl side of proline residues, is involved in the breakdown of several proline-containing neuropeptides and, thus, may contribute to the regulation of behavioral activities. In this study, the distribution of PEP mRNA was investigated in the central nervous system and pituitary of rat by means of quantitative reverse transcriptase-polymerase chain reaction analysis and in situ hybridization histochemistry. High densities of PEP transcripts were found in cerebellar Purkinje and granule cells, within most hypothalamic nuclei, in pyramidal neurons of the Ammon's horn, in granule cells of the dentate gyrus, and within the basolateral complex of the amygdala. Moderate levels of PEP mRNA were observed in layers 3-5 of the cerebral cortex, the anterior thalamic group, the septal region, the substantia nigra, the magnocellular neurons of the red nucleus, and the motor nuclei of the cranial nerves. Low concentrations of PEP mRNA were detected in the deep mesencephalic nuclei, the reticular formation, the pretectum, and the tectum. A high density of PEP mRNA was found in the intermediate and the anterior lobes of the pituitary, while the neural lobe was devoid of labeling. In several brain regions, the distribution pattern of PEP mRNA overlapped that of various neuropeptide receptors, suggesting that PEP is actually involved in the inactivation of regulatory neuropeptides.

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“…In mammals, three different types of PEP enzyme have been reported: cytoplasmic [38], serum [39], and membrane [40]. This section will focus solely on the cytoplasmic PEP, as its biology has been most extensively studied.…”

Section: Physiologymentioning

confidence: 99%

Prolyl endopeptidases

Gass

Khosla

2006

Cell. Mol. Life Sci.

120

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This review describes the structure and function of prolyl endopeptidase (PEP) enzymes and how they are being evaluated as drug targets and therapeutic agents. The most well studied PEP family has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain to hydrolyze the peptide bond on the carboxyl side of internal proline residues of an oligopeptide substrate. Structural and functional studies on this protease family have elucidated the mechanism for peptide entry between the two domains. Other structurally unrelated PEPs have been identified, but have not been studied in detail. Human PEP has been evaluated as a pharmacological target for neurological diseases due to its high brain concentration and ability to cleave neuropeptides in vitro. Recently, microbial PEPs have been studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten.

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Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain

Cited by 42 publications

References 24 publications

Ontogeny of Soluble and Particulate Prolyl Endopeptidase Activity in Several Areas of the Rat Brain and in the Pituitary Gland

Ontogeny of Soluble and Particulate Prolyl Endopeptidase Activity in Several Areas of the Rat Brain and in the Pituitary Gland

Localization of the mRNA encoding prolyl endopeptidase in the rat brain and pituitary

Prolyl endopeptidases

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