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

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.

Localization and subcellular distribution of prolyl oligopeptidase in the mouse placenta

“…This role of POP was first suggested by the finding that a specific POP inhibitor, ZTTA, inhibited DNA synthesis in the cultured cells of flesh fly and mouse and POP was localized to the nuclei in the cells (Ishino et al, 1998;Ohtsuki et al, 1997). Some of the recent studies also support this function by showing that POP was localized to the nucleus in proliferating or differentiating cells (Hannula et al, 2010;Moreno-Baylach et al, 2008). However, no particular mechanisms have yet been suggested, so it may also be possible that the cytoplasmic and membrane-associated POP could participate in cell cycle regulation.…”

“…In fact, a very recent report showed that POP was localized to the nucleus only early in the brain development (Hannula et al, 2010). Although there is no conclusive evidence for the nuclear POP controlling the cell cycle, it is widely accepted that POP plays some important roles in development and differentiation.…”

Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells

“…In mammals, it is expressed in a wide variety of tissues, including the ovary, brain, liver, testis, kidney, thymus, breast, stomach, prostate gland, and spleen (Goossens, De Meester, Vanhoof, & Scharpé, ; Myöhänen, Pyykkö, Männistö, & Carpen, ). POP participates in the regulation of a comprehensive range of physiological or pathological processes by affecting cell proliferation (Matsubara, Ono, Tsubuki, Irie, & Kawashima, ; Suzuki, Sakaguchi, Tanaka, Yoshimoto, & Takaoka, ), differentiation (Hannula, Mannisto, & Myohanen, ; Matsubara et al, ), apoptosis (Matsuda, Sakaguchi, Tanaka, Yoshimoto, & Takaoka, ), and hydrolyzing extracellular polypeptides (Matsuda et al, ). In the central nervous system, POP plays an important role in learning and memory.…”

The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients

“…In the mature healthy brain, PREP is highly expressed in a certain group of neurons in well-defined areas such as the striatum, cortex, hippocampus and cerebellum but scarcely detectable in glial cells [ 13 , 14 ]. PREP has been associated to neurodegeneration [ 10 , 11 ], proliferation [ 15 ], neuronal differentiation [ 16 ], development [ 17 , 18 ] and also to inflammation [ 19 – 21 ]. PREP levels have been found altered in Alzheimer’s (AD), Parkinson’s (PD) [ 22 ] and Huntington’s (HD) diseases (reviewed in [ 10 ]).…”