Disease relevance of Serpine2

• We show here that synthetic peptide inhibitors with thrombin specificity mimic GDN at similar concentrations in neuroblastoma cells [1].
• In vitro CpG methylation blocked transcription from the GDN/PN-1 promoter in rat hepatoma cells but not in C6 rat glioma cells [2].
• Using semi-quantitative reverse transcription-polymerase chain reaction analysis, we show that prothrombin was up-regulated in the hippocampal formation 24 h after transient global ischemia in rats (two-vessel occlusion with hypotension), whereas the expression of PN-1 and the expression of PAR-subtypes 1-3 did not change significantly [3].
• These results further support the suggestion that GDN is important for axonal regeneration in vivo, and indicate that protease inhibitors could have a role in Wallerian degeneration and peripheral nerve regeneration [4].
• Levels of both PN-1 and thrombin are increased in the brain in response to insults such as ischemia, suggesting roles in neural injury and repair processes [5].

High impact information on Serpine2

• GDN can promote neurite outgrowth in vitro from neuroblastoma cells, sympathetic neurons and hippocampal neurons (L. Farmer et al., manuscript in preparation) [4].
• Here we report that after lesion of the rat sciatic nerve there is a large transient increase in the amount of GDN messenger RNA and of released GDN [4].
• Glia-derived nexin (GDN), also known as protease nexin I, is a serine protease inhibitor of deduced relative molecular mass 41,700, identified in conditioned media of glioma cells by its neurite-promoting activity [4].
• A 1 min exposure of PC12 cells to interferon-gamma also causes PN1 gene induction, suggesting that the "triggered" NGF and interferon-gamma signaling pathways share common molecular intermediates [6].
• Whereas continuous exposure to NGF causes the induction of a family of sodium channels, the effect of a brief exposure is to induce selectively expression of the peripheral nerve-type sodium channel gene PN1, through a distinct signaling pathway requiring immediate-early genes [6].

Chemical compound and disease context of Serpine2

• Glia-derived nexin (GDN) is a 43-kDa glycoprotein isolated from rat glioma cell cultures [7].

Biological context of Serpine2

• Point mutations in the E-box binding site which abolish USF binding in vitro increase the transcriptional activity of the PN-1 promoter [8].
• A strong negative regulatory element has been shown by the missing nucleoside technique to be a CACGTG site (E-box) in the proximal part of the PN-1 promoter [8].
• The 5'-flanking sequence and the first exon were found to be GC-rich, indicating that the 5' region of the rat GDN/PN-1 gene resides within a CpG island [2].
• The presence of these consensus sequences is consistent with the known expression pattern of GDN/PN-1 [2].
• The first three exons and the promoter of rat glia-derived nexin, also called protease nexin-1 (GDN/PN-1), have been identified through analysis of rat genomic clones [2].

Anatomical context of Serpine2

• All of the effects of thrombin on astrocytes and neurons were blocked by the brain thrombin inhibitor, protease nexin-1 (PN-1) [9].
• These results indicate that thrombin and PN-1 may regulate the viability of both astrocytes and neurons in early moments following trauma to the CNS or other conditions that alter the blood-brain barrier [9].
• The expression of the serine protease inhibitor Protease nexin-1 (PN-1) is upregulated in glial cells following different types of lesion in the nervous system [8].
• In chick sympathetic neurons, GDN but not hirudin and synthetic peptide inhibitors promoted neurite outgrowth (Zurn et al., 1988) [1].
• We examined the effect of thrombin on PN-1 expression by rat aortic smooth muscle cells (RASMCs) [10].

Associations of Serpine2 with chemical compounds

• A lower amount of PN-1 was released by heparin from TRAP-stimulated versus unstimulated cells and correlated with a decreased capacity to inhibit thrombin [10].
• Protease nexin-1 (PN-1), a potent inhibitor of serine proteases, is present in vascular cells and forms complexes with thrombin, plasminogen activators, and plasmin [10].
• Pre-treatment of smooth muscle cells with cycloheximide abolished the reduction of PN-1 expression by thrombin [10].
• These antibodies stain a single band at 43 kd on immunoblots of concentrated C6 glioma-conditioned medium and have been used to demonstrate that GDN is present in the olfactory system of the rat [11].
• Displacement of Ang II binding using the selective ligands losartan and CGP 42112 led to a severalfold increase of PN-1 protein and mRNA over basal levels, indicating that the observed effect was mediated by specific binding sites [12].

Regulatory relationships of Serpine2

• This effect was mediated via the interaction of thrombin with its receptor protease activated receptor (PAR-1) since the peptide thrombin receptor activating peptide (TRAP) reduced PN-1 expression [10].

Other interactions of Serpine2

• The expression of PAR1 and the potent thrombin inhibitor protease nexin-1 (PN-1) was investigated in the developing rat brain and spinal cord and after peripheral nerve lesion [13].
• Of the cDNAs, the p112 regulatory subunit of the 26S proteasome, a PDGF-associated protein and the glia-derived protease nexin PN-1 could be identified [14].

Analytical, diagnostic and therapeutic context of Serpine2

• PN-1 expression was determined by measuring protein and mRNA levels, using respectively immunoblotting and semi-quantitative reverse transcriptase polymerase chain reaction (PCR) [10].
• The expression pattern of the serine protease inhibitor gene Protease nexin-1 (PN-1) has been analyzed by in situ hybridization during embryonic nervous system development [15].
• At PN1 and PN3 immunofluorescence microscopy revealed weak labelling, mainly in radial processes (Bergmann fibres) and at the pial surface [16].
• Relative to the two control groups, the low iron group weighed less on PN1, and this weight difference persisted in adulthood [17].
• Dissections were taken from male and female rat pups on the day of birth (postnatal day 0; PN 0), PN1, PN5, PN11 or PN20 [18].

References