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

Histochemie (Impact Factor: 3.05). 11/2008; 130(5):993-1003. DOI: 10.1007/s00418-008-0468-x


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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    • "More recently , POP was found in various cell types in both the cytoplasm and nuclei in mouse whole-body sections and at the cellular level in peripheral tissues by immunohistochemical study. The nuclear colocalization of the POP protein and Ki-67, a proliferation marker protein, suggested that POP is involved in cell proliferation [10]. "
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    ABSTRACT: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G0/G1 cell cycle arrest and increased levels of the CDK inhibitor p27(kip1) and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-({4-[2-(E)-styrylphenoxy] butanoyl}-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G0/G1 cell cycle phase arrest and increased levels of p27(kip1) in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G0 state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.
    Biochemical and Biophysical Research Communications 11/2013; 443(1). DOI:10.1016/j.bbrc.2013.11.051 · 2.30 Impact Factor
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    • "In earlier studies, PREP has been suggested to participate in mouse sperm motility (Kimura et al. 2002), and we have detected high PREP amounts in the mouse testis (Myöhänen et al. 2008b). In humans, we also detected high amounts of PREP in several cell types involved in spermatogenesis , particularly in the early phase. "
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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 · 1.96 Impact Factor
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    • "The activity of PEP is higher in developing than in adult tissues [8]. In addition, its nuclear localization in proliferating (peripheral) tissues seems to link this enzyme in proliferation and differentiation of the tissues [10]. "
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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 · 1.83 Impact Factor
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