Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues

Histochemie (Impact Factor: 2.93). 11/2008; 130(5):993-1003. DOI: 10.1007/s00418-008-0468-x

ABSTRACT Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline-containing peptides shorter than 30-mer, including
many bioactive peptides. The distribution of POP in the brain has been studied but little is known about the distribution
of peripheral POP. We used immunohistochemistry to localize POP in mouse whole-body sections and at the cellular level in
peripheral tissues. Furthermore, we used a POP activity assay to reveal the associations between POP protein and its enzymatic
activity. The highest POP protein densities were found in brain, kidney, testis and thymus, but in the liver the amounts of
POP protein were small. There were remarkable differences between the distribution of POP protein and activity. The highest
POP activities were found in the liver and testis while kidney had the lowest activity. In peripheral tissues, POP was present
in various cell types both in the cytoplasm and nucleus of the cells, in contrast to the brain where no nuclear localization
was detected. These findings support the proposed role of POP in cell proliferation in peripheral tissues. The dissociation
of the distribution of POP protein and its enzymatic activity points to nonhydrolytic functions of POP and to strict endogenous
regulation of POP activity.

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    ABSTRACT: Prolyl oligopeptidase (PREP) is a serine protease that hydrolyzes peptides shorter than 30-mer, and it has been connected with multiple physiological and pathological conditions. PREP has been mostly studied in the brain, but significant PREP activities have been measured in peripheral tissues. Moreover, increased PREP activities have been found in tumors. In this study, the authors studied the immunohistochemical distribution of PREP protein in human peripheral tissues and in ovarian and colorectal tumors. PREP was found to be widely distributed in human peripheral tissues and specifically in certain cells. The most intense PREP expression was seen in the testis, ovaries, liver, and some parts of the skin. At the cellular level, high PREP levels were seen as a rule in secreting epithelial cells and cells involved in reproduction. Increased PREP expression was seen in most of the tumors studied. PREP expression was higher in malignant than benign tumors, and in ovarian epithelial cancers, there was a trend for increased PREP staining with increased malignancy grade. Results suggest that PREP may be associated with secretory processes as well as in reproduction. A more abundant expression of PREP in malignant than benign tumors suggests that PREP may be associated with expansion and metastasis of tumors.
    Journal of Histochemistry and Cytochemistry 06/2012; 60(9):706-15. DOI:10.1369/0022155412453051 · 2.40 Impact Factor
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    ABSTRACT: Prolyl endopeptidase (EC (PEP) is a serine peptidase that converts several biologically active peptides. This enzyme has been linked to several neurological, digestive, cardiovascular and infectous disorders. However, little is known about its involvement in neoplastic processes. This study analyzes fluorimetrically cytosolic and membrane-bound PEP activity in a large series (n=122) of normal and neoplastic tissues from the kidney, colon, oral cavity, larynx, thyroid gland and testis. Cytosolic PEP activity significantly increased in clear cell renal cell carcinoma, urothelial carcinoma of the renal pelvis and head and neck squamous cell carcinoma. Both cytosolic and membrane-bound PEP activity were also increased in colorectal adenomatous polyps. These data suggest the involvement of PEP in some mechanisms that underlie neoplastic processes.
    Regulatory Peptides 03/2010; 163(1-3):102-6. DOI:10.1016/j.regpep.2010.03.012 · 2.01 Impact Factor
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    ABSTRACT: Catechol-O-methyltransferase (COMT) has both soluble (S-COMT) and membrane-bound (MB-COMT) isoforms. A specific COMT antibody was used in immunohistochemical and confocal co-localization studies to explore the distribution of COMT in general in normal mice and MB-COMT in particular, in an S-COMT deficient mouse line. In the peripheral tissues, high COMT protein and activity levels were observed in liver and kidney, whereas in the brain, COMT expression and activity were much lower. MB-COMT was widely distributed throughout all tissues, and overall, the MB-COMT distribution mimicked the distribution of S-COMT. MB-COMT displayed some preference for brain tissue, notably in the hippocampus. MB-COMT related enzymatic activity was also pronounced in the cerebral cortical areas and hypothalamus. MB-COMT, like S-COMT, was found to be an intracellular enzyme but it was not associated with plasma membranes in the brain. Both COMT forms were abundantly found in microglial cells and intestinal macrophages, but also in astroglial cells. COMT was also present in some neuronal cells, like pyramidal neurons, cerebellar Purkinje and granular cells and striatal spiny neurons, but not in major long projection neurons. Finally, it seemed that nuclear COMT is not visible in S-COMT deficient mice.
    Journal of Neurochemistry 03/2010; 113(6):1632-43. DOI:10.1111/j.1471-4159.2010.06723.x · 4.24 Impact Factor