Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro

Abstract

Membrane-associated glycoprotein neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play an important role in brain plasticity by regulating cell-cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using a SH-SY5Y neuroblastoma cell line with stable overexpression of PREP, we found a remarkable loss of PSA-NCAM, reduced levels of NCAM180 and NCAM140 protein species, and a significant increase in the NCAM immunoreactive band migrating at an apparent molecular weight of 120 kDa in PREP-overexpressing cells. Moreover, increased levels of NCAM fragments were found in the concentrated medium derived from PREP-overexpressing cells. PREP overexpression selectively induced an activation of matrix metalloproteinase-9 (MMP-9), which could be involved in the observed degradation of NCAM, as MMP-9 neutralization reduced the levels of NCAM fragments in cell culture medium. We propose that increased PREP levels promote epidermal growth factor receptor (EGFR) signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for newlydiscovered roles for PREP in mechanisms regulating cellular plasticity through NCAM and PSA-NCAM.

Prolyl endopeptidase gene disruption attenuates high fat diet-induced nonalcoholic fatty liver disease in mice by improving hepatic steatosis and inflammation

“…Our study demonstrates that MMP9 is significantly decreased in the HFD-PREP gt mice. Previous studies indicated that PREP could regulate the activity of extracellular MMP9 (29,35). Notably, the production of PGP was obviously suppressed in the HFD-PREP gt mice.…”

The intact parasympathetic nerve promotes submandibular gland regeneration through ductal cell proliferation

“…Jaako K et al indicate that the PST protein nucleus expression was also found in the wild-type neuroblastoma cells. 35 However, in the denervation group, the level of NCAM expression decreased during the regeneration process. In contrast, the level of PST expression increased after deligation and remained high at day 28.…”

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

“…THY1 (Thy-1 Cell Surface Antigen) has previously been shown to be downregulated in NP compared to AF and upregulated with age, where THY1-cell interactions can result in focal adhesion formation. 60,117 Similarly, ANGPT1, FAP (Prolyl endopeptidase FAP), CADM1, and CDON have been associated with cytoskeletal reorganization, cell-ECM and cell-cell interactions, as well as involvement in mechanosensitive intracellular signaling pathways in cell types including NP and AF cells [118][119][120][121][122][123][124][125][126][127][128][129][130]. One of the most highly enriched downregulated gene sets was Vacuolar Lumen, where many genes are associated with lysosomal activity.…”