title: Regulation of protease nexin-1 synthesis and secretion in cultured brain cells by injury-related factors.
abstract: The clotting protease thrombin might contribute to cell damage following brain injury by its ability to retract processes on neurons and astrocytes. Protease nexin-1 (PN-1), a potent inhibitor of thrombin, is localized around cerebral blood vessels where it may protect these cells from extravasated thrombin during injury or alteration of the blood-brain barrier. Here we examined the effects of several injury-related factors on the regulation of PN-1 in cultured brain cells. Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta stimulated the secretion of PN-1 by the neuroblastoma cell line SK-N-SH. This cell line comprises both neuronal and glial cells. Analyses using cloned derivatives of these two cell types showed that PN-1 was secreted by the glial cells; PN-1 secretion was stimulated 90-fold by interleukin-1, 15-fold by tumor necrosis factor-alpha, 10-fold by tumor growth factor-beta, and 4-fold by platelet-derived growth factor. Measurements of newly synthesised PN-1 demonstrated that these factors produced an equivalent stimulation of PN-1 synthesis. The neuronal cells secreted two thrombin-binding proteins distinct from PN-1. Interactions between these two cell types regulated the secretion of PN-1 and the two thrombin-binding proteins.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
authors.forename: P J
authors.initials: PJ
authors.lastname: Vaughan
authors.forename: D D
authors.initials: DD
authors.lastname: Cunningham
mesh_terms: D016564:Amyloid beta-Protein Precursor; D001932:Brain Neoplasms; D002352:Carrier Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D009447:Neuroblastoma; D009457:Neuroglia; D009474:Neurons; D015849:Plasminogen Inactivators / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D058258:Serpin E2; D013917:Thrombin / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D007375:Interleukin-1; D015849:Plasminogen Inactivators; D010982:Platelet-Derived Growth Factor; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin