A glia-derived neurite-promoting factor with protease inhibitory activity.

Abstract

Brain cells and glioma cells in culture release a protein which induces neurite outgrowth in neuroblastoma cells. This neurite‐promoting factor (NPF), which has been purified from serum‐free glioma conditioned medium, has an apparent mol. wt. of 43 000. NPF inhibits urokinase as well as plasminogen activator‐dependent caseinolysis or fibrinolysis. NPF and urokinase form an SDS‐resistant complex. The fact that this glia‐derived NPF is a potent protease inhibitor indicates that glial cells modulate the proteolytic activity associated with neuronal cells and suggests that this phenomenon is one of the biochemical events involved in the regulation of neurite growth.

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

“…In several cases, we observed that a fraction of the labelled uPA migrated with an apparent molecular size larger than that of the Mr 33 000 free enzyme (lane 1). In view of the known ability of uPA to form SDS-resistant complexes with different serpin-class antiproteases (Baker et al, 1980;Vassalli et al, 1984) (Baker et al, 1980;Guenther et al, 1985;Stone et al, 1987). Likewise, the uPA ligand in seminal vesicle could be quantitatively adsorbed on heparin -Sepharose, and eluted using a salt gradient at -0.5 M NaCl (not shown).…”

“…PN-l is secreted by the adult mouse seminal vesicle Cultured human fibroblasts and rat glioma cells release PN-I into the medium (Baker et al, 1980;Guenther et al, 1985). To determine whether PN-I is present in the seminal vesicle secretory product, the amounts of PN-I in an extract of glandular tissue ( Figure 5, lanes 5 and 6) and in the liquid secretion (lanes 7 and 8) were compared with that in an unfractionated extract (lanes 2-4).…”

“…We have identified this ligand as protease nexin I (PN-I), a serpin released by human fibroblasts (Baker et al, 1980) and identical to glia-derived nexin (GDN) (Gloor et al, 1986;Sommer et al, 1987;McGrogan et al, 1988), first detected as a factor promoting neurite outgrowth in vitro (Guenther et al, 1985) that is found in different structures of the nervous system (Reinhard et al, 1988;Meier et al, 1989). PN-I reacts with and inhibits thrombin, uPA, tissuetype PA (tPA), trypsin and plasmin (Baker et al, 1980;Eaton and Baker, 1983;Guenther et al, 1985;Stone et al, 1987). In addition, we have shown that the abundance of PN-I protein and mnRNA in the mouse seminal vesicle is under androgen control.…”

Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation

“…Unlike the coagulation /fibrinolytic pathway where several different inhibitors are known, in the CNS only protease nexin-1 (PN-1; Guenther et al, 1985;Sommer et al, 1987) is present at significant levels (Mansuy et al, 1993;Sappino et al, 1993;Reinhard et al, 1994). PN-1 is expressed in both glial and neuronal cells of the developing and adult CNS (Mansuy et al, 1993;Sappino et al, 1993;Reinhard et al, 1994) and in glomeruli of the olfactory bulbs, where synapse formation and elimination remain an active process throughout life (Reinhard et al, 1988;Mansuy et al, 1993).…”

Olfactory ensheathing cells: Historical perspective and therapeutic potential

“…Both OECs and astrocytes within the NFL of the olfactory bulb also express protease nexin-1 (PN-1; Reinhard et al, 1988;Scotti et al, 1994), whereas astrocytes elsewhere in the CNS do not express this enzyme. PN-1 has been demonstrated to function as a chemotropic factor for neurites in vitro (Monard et al, 1973;Guenther et al, 1985;Zurn et al, 1988) and could potentially be functioning in the same manner within the primary olfactory pathway.…”