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Original Paper

Sequential Expression, Activity and Nuclear Localization of Prolyl Oligopeptidase Protein in the Developing Rat Brain

Hannula M.J. · Männistö P.T. · Myöhänen T.T.

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Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland

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Dev Neurosci 2011;33:38–47

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 24, 2010
Accepted: October 14, 2010
Published online: December 14, 2010
Issue release date: April 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

Abstract

Prolyl oligopeptidase (POP) is a serine protease that hydrolyzes peptides shorter than 30-mer. Some evidence has recently been obtained that POP can generate protein-protein interactions and therefore participate in various physiological and pathological events. Several studies have reported that POP may be involved in neurogenesis since its activity increases during development and can be found in the nucleus of proliferating tissues. In cell cultures, POP has been shown to be localized in the nucleus, but only early in the development, since during maturation it is moved to the cytosol. We have now studied for the first time the expression of POP protein, its enzymatic activity and nuclear localization in vivo in the developing rat brain. We observed that enzymatic activity of POP is highest on embryonic day 18 while the protein amounts reach their peak at birth. Furthermore, POP is located in the nucleus only early in the development but is transferred to the cytosol already before parturition. Our in vivo results confirm the previous cell culture results supporting the role of POP in neurogenesis. A discordance of antenatal protein amounts and enzymatic activities is suggesting a tight regulation of POP activity and possibly even a nonhydrolytic role at that stage.

© 2010 S. Karger AG, Basel


References

  1. Rawlings ND, Barrett AJ: Families of serine peptidases. Methods Enzymol 1994;244:19–61.
  2. Venäläinen JI, Juvonen RO, Männistö PT: Evolutionary relationships of the prolyl oligopeptidase family enzymes. Eur J Biochem 2004;271:2705–2715.
  3. Polgar L: Prolyl oligopeptidases. Methods Enzymol 1994;244:188–200.
  4. Goossens F, De Meester I, Vanhoof G, Scharpe S: Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids. Eur J Clin Chem Clin Biochem 1996;34:17–22.
  5. Fuse Y, Polk DH, Lam RW, Reviczky AL, Fisher DA: Distribution and ontogeny of thyrotropin-releasing hormone degrading enzymes in rats. Am J Physiol 1990;259:E787–E791.
  6. Kato T, Okada M, Nagatsu T: Distribution of post-proline cleaving enzyme in human brain and the peripheral tissues. Mol Cell Biochem 1980;32:117–121.
  7. Agirregoitia N, Casis L, Gil J, Ruiz F, Irazusta J: Ontogeny of prolyl endopeptidase and pyroglutamyl peptidase I in rat tissues. Regul Pept 2007;139:52–58.
  8. Bellemere G, Vaudry H, Mounien L, Boutelet I, Jegou S: Localization of the mRNA encoding prolyl endopeptidase in the rat brain and pituitary. J Comp Neurol 2004;471:128–143.
  9. Myöhänen TT, Garcia-Horsman JA, Tenorio-Laranga J, Männistö PT: Issues about the physiological functions of prolyl oligopeptidase based on its discordant spatial association with substrates and inconsistencies among mRNA, protein levels, and enzymatic activity. J Histochem Cytochem 2009;57:831–848.
  10. Garcia-Horsman JA, Männistö PT, Venäläinen JI: On the role of prolyl oligopeptidase in health and disease. Neuropeptides 2007;41:1–24.
  11. Huston JP, Hasenohrl RU: The role of neuropeptides in learning: focus on the neurokinin substance P. Behav Brain Res 1995;66:117–127.
  12. Cunningham DF, O’Connor B: Proline specific peptidases. Biochim Biophys Acta 1997;1343:160–186.
  13. Brandt I, Scharpe S, Lambeir AM: Suggested functions for prolyl oligopeptidase: a puzzling paradox. Clin Chim Acta 2007;377:50–61.
  14. Männistö PT, Venäläinen JI, Jalkanen AJ, Garcia-Horsman JA: Prolyl oligopeptidase: a potential target for the treatment of cognitive disorders. Drugs News Persp 2007;20:293–305.
  15. Laitinen KS, van Groen T, Tanila H, Venäläinen J, Männistö PT, Alafuzoff I: Brain prolyl oligopeptidase activity is associated with neuronal damage rather than beta-amyloid accumulation. Neuroreport 2001;12:3309–3312.
  16. Agirregoitia N, Gil J, Ruiz F, Irazusta J, Casis L: Effect of aging on rat tissue peptidase activities. J Gerontol A Biol Sci Med Sci 2003;58:B792–B797.
  17. Maes M, Goossens F, Scharpe S, Calabrese J, Desnyder R, Meltzer HY: Alterations in plasma prolyl endopeptidase activity in depression, mania, and schizophrenia: effects of antidepressants, mood stabilizers, and antipsychotic drugs. Psychiatry Res 1995;58:217–225.
  18. Maes M, Goossens F, Scharpe S, Meltzer HY, D’Hondt P, Cosyns P: Lower serum prolyl endopeptidase enzyme activity in major depression: further evidence that peptidases play a role in the pathophysiology of depression. Biol Psychiatry 1994;35:545–552.
  19. Mantle D, Falkous G, Ishiura S, Blanchard PJ, Perry EK: Comparison of proline endopeptidase activity in brain tissue from normal cases and cases with Alzheimer’s disease, Lewy body dementia, Parkinson’s disease and Huntington’s disease. Clin Chim Acta 1996;249:129–139.
  20. Toide K, Iwamoto Y, Fujiwara T, Abe H: JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. J Pharmacol Exp Ther 1995;274:1370–1378.
  21. Toide K, Shinoda M, Miyazaki A: A novel prolyl endopeptidase inhibitor, JTP-4819 – its behavioral and neurochemical properties for the treatment of Alzheimer’s disease. Rev Neurosci 1998;9:17–29.
  22. Puttonen KA, Lehtonen S, Raasmaja A, Männistö PT: A prolyl oligopeptidase inhibitor, Z-Pro-Prolinal, inhibits glyceraldehyde-3-phosphate dehydrogenase translocation and production of reactive oxygen species in CV1-P cells exposed to 6-hydroxydopamine. Toxicol In Vitro 2006;20:1446–1454.
  23. Williams RS, Cheng L, Mudge AW, Harwood AJ: A common mechanism of action for three mood-stabilizing drugs. Nature 2002;417:292–295.
  24. Cheng L, Lumb M, Polgar L, Mudge AW: How can the mood stabilizer VPA limit both mania and depression? Mol Cell Neurosci 2005;29:155–161.
  25. Schulz I, Zeitschel U, Rudolph T, Ruiz- Carrillo D, Rahfeld JU, Gerhartz B, Bigl V, Demuth HU, Rossner S: Subcellular localization suggests novel functions for prolyl endopeptidase in protein secretion. J Neurochem 2005;94:970–979.
  26. Agirregoitia N, Irazusta A, Ruiz F, Irazusta J, Gil J: Ontogeny of soluble and particulate prolyl endopeptidase activity in several areas of the rat brain and in the pituitary gland. Dev Neurosci 2003;25:316–323.
  27. Kato T, Nakano T, Kojima K, Nagatsu T, Sakakibara S: Changes in prolyl endopeptidase during maturation of rat brain and hydrolysis of substance P by the purified enzyme. J Neurochem 1980;35:527–535.
  28. Ohtsuki S, Homma K, Kurata S, Komano H, Natori S: A prolyl endopeptidase of Sarcophaga peregrina (flesh fly): its purification and suggestion for its participation in the differentiation of the imaginal discs. J Biochem (Tokyo) 1994;115:449–453.
  29. Daly DJ, Maskrey P, Pennington RJ: Characterization of proline endopeptidase from skeletal muscle. Int J Biochem 1985;17:521–524.
  30. Ishino T, Ohtsuki S, Homma K, Natori S: cDNA cloning of mouse prolyl endopeptidase and its involvement in DNA synthesis by Swiss 3T3 cells. J Biochem (Tokyo) 1998;123:540–545.
  31. Agirregoitia N, Bizet P, Agirregoitia E, Boutelet I, Peralta L, Vaudry H, Jegou S: Prolyl endopeptidase mRNA expression in the central nervous system during rat development. J Chem Neuroanat 2010;40:53–62.
  32. Moreno-Baylach MJ, Felipo V, Männistö PT, Garcia-Horsman JA: Expression and traffic of cellular prolyl oligopeptidase are regulated during cerebellar granule cell differentiation, maturation, and aging. Neuroscience 2008;156:580–585.
  33. Venäläinen JI, Juvonen RO, Forsberg MM, Garcia-Horsman A, Poso A, Wallen EA, Gynther J, Männistö PT: Substrate-dependent, non-hyperbolic kinetics of pig brain prolyl oligopeptidase and its tight binding inhibition by JTP-4819. Biochem Pharmacol 2002;64:463–471.
  34. Myöhänen TT, Venäläinen JI, Garcia-Horsman JA, Piltonen M, Männistö PT: Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues. Histochem Cell Biol 2008;130:993–1003.
  35. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.
  36. Myöhänen TT, Venäläinen JI, Tupala E, Garcia-Horsman JA, Miettinen R, Männistö PT: Distribution of immunoreactive prolyl oligopeptidase in human and rat brain. Neurochem Res 2007;32:1365–1374.
  37. Venäläinen JI, Garcia-Horsman JA, Forsberg MM, Jalkanen A, Wallen EA, Jarho EM, Christiaans JA, Gynther J, Männistö PT: Binding kinetics and duration of in vivo action of novel prolyl oligopeptidase inhibitors. Biochem Pharmacol 2006;71:683–692.
  38. Myöhänen TT, Venäläinen JI, Garcia-Horsman JA, Piltonen M, Männistö PT: Cellular and subcellular distribution of rat brain prolyl oligopeptidase and its association with specific neuronal neurotransmitters. J Comp Neurol 2008;507:1694–1708.
  39. Paxinos G: The Rat Nervous System. San Diego, Elsevier Academic Press, 2004.
  40. Ohtsuki S, Homma K, Kurata S, Natori S: Nuclear localization and involvement in DNA synthesis of Sarcophaga prolyl endopeptidase. J Biochem (Tokyo) 1997;121:1176–1181.
  41. Brandt I, Gerard M, Sergeant K, Devreese B, Baekelandt V, Augustyns K, Scharpe S, Engelborghs Y, Lambeir AM: Prolyl oligopeptidase stimulates the aggregation of alpha-synuclein. Peptides 2008;29:1472–1478.
  42. Di Daniel E, Glover CP, Grot E, Chan MK, Sanderson TH, White JH, Ellis CL, Gallagher KT, Uney J, Thomas J, Maycox PR, Mudge AW: Prolyl oligopeptidase binds to GAP-43 and functions without its peptidase activity. Mol Cell Neurosci 2009;41:373–382.
  43. Yoshimoto T, Tsukumo K, Takatsuka N, Tsuru D: An inhibitor for post-proline cleaving enzyme: distribution and partial purification from porcine pancreas. J Pharmacobiodyn 1982;5:734–740.
  44. Yamakawa N, Shimeno H, Soeda S, Nagamatsu A: Regulation of prolyl oligopeptidase activity in regenerating rat liver. Biochim Biophys Acta 1994;1199:279–284.
  45. Salers P: Evidence for the presence of prolyl oligopeptidase and its endogenous inhibitor in neonatal rat pancreatic beta-cells. Regul Pept 1994;50:235–245.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 24, 2010
Accepted: October 14, 2010
Published online: December 14, 2010
Issue release date: April 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE


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