Neurite outgrowth activity of protease nexin‐1 on neuroblastoma cells requires thrombin inhibition

David Gurwitz, Dennis D. Cunningham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Protease nexin‐1 (PN‐1) is a protein proteinase inhibitor recently shown to be identical with the glial‐derived neurite‐promoting factor or glial‐derived nexin. It has been shown to promote neurite outgrowth in neuroblastoma cells and in sympathetic neurons. The present experiments were designed to further test the hypothesis that this activity on neuroblastoma cells is due to its ability to complex and inhibit thrombin. It has been suggested that PN‐1 :thrombin complexes might mediate the neurite outgrowth activity of PN‐1. However, the present studies showed that such complexes, unlike free PN‐1, did not promote neurite outgrowth. The neurite outgrowth activity of PN‐1 was only detected in the presence of thrombin or serum (which contains thrombin). PN‐1 did not affect the rate or extent of neurite outgrowth that occurred when neuroblastoma cells were placed in serum‐free medium. Retraction of neurites by thrombin was indistinguishable in cells whose neurites had been extended in the presence or absence of PN‐1. The neurite‐promoting activity of PN‐1 was inhibited by an anti‐PN‐1 monoclonal antibody, which blocks its capacity to complex serine proteinases. The plasma thrombin inhibitor, antithrombin III, stimulated neurite outgrowth but only when its thrombin inhibitory activity was accelerated by heparin. The neurite outgrowth activity of both antithrombin III and PN‐1 corresponded to their inhibition of thrombin. Together, these observations show that PN‐1 promotes neurite outgrowth from neuroblastoma cells by inhibiting thrombin and suggest that this depends on the ability of thrombin to retract neurites.

Original languageEnglish
Pages (from-to)155-162
Number of pages8
JournalJournal of Cellular Physiology
Volume142
Issue number1
DOIs
StatePublished - Jan 1990
Externally publishedYes

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