Journal of Histochemistry and Cytochemistry, Vol. 47, 1647-1647, December 1999, Copyright © 1999, The Histochemical Society, Inc.


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19 Proprotein convertases (PCs) in degenerating/regenerating peripheral nerves.

M. Marcinkiewicza
a Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, QC H2W 1R7 Canada

Injured peripheral nerves de novo synthesize multiple precursor proteins, which after post-translational processing, give raise to the active moieties involved in the regeneration of damaged tissues. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are good examples of such proteins. Both proNGF and proBDNF require posttranslational processing by mammalian proprotein convertases (PCs) belonging to the family of subtilisin/kexin-like enzymes that cleave at specific sites composed of the basic residues Arg and Lys. In this work, we analyzed the spatial and temporal patterns of distribution of the following PCs: furin, PC1, PC2, PACE4, PC5 and PC7 in the distal stump of the rat sciatic nerve cut for different time-intervals (5 min. to 14 days), in cultured nerve segments, and cultured Schwann cells. We compared their expression patterns to that of NGF and BDNF. The results provided in vivo evidence of the presence of specific PCs in the injured nerves. Based on both abundance and colocalization criteria, we found an association between NGF, furin, PC5 and PC7 within infiltrating macrophages and perivascular smooth muscle cells observed in the perineurium shortly after injury (1 to 24 hours) or in cultured nerves. In addition, association of BDNF and PC1 was observed in endoneurial Schwann cells in vivo during late phase following nerve transection (4 to 7 days). Coexpression of exogenous neurotrophins by infection with vaccinia vector showed that proNGF and proBDNF are cleaved by PCs on smaller molecular forms in cultured Schwann cells. This work provided in vivo and ex vivo evidence suggesting the involvement of PCs in the activation of neurotrophin precursors during nerve regeneration. Refs: Marcinkiewicz et al., Mol. Brain Res. 59: 229-246, 1998; Marcinkiewicz et al., J. Comp. Neurol. 403: 471-485, 1999.





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