title: The pro-protein convertase PC1 is induced in the transected sciatic nerve and is present in cultured Schwann cells: comparison with PC5, furin and PC7, implication in pro-BDNF processing.
abstract: Injury of peripheral nerves induces expression of several pro-protein convertases (PCs) involved in processing of precursor proteins into their diverse active end-products. In this study, the focus was on convertase PC1 which, although undetectable in control nerves, is strongly induced in injured nerves. High concentrations of PC1 mRNA of 9.0, 5.5, 3.0, 2.5 and 1.6 kb were observed on day 4 post-lesion in proximal and distal segments. By in situ hybridization PC1 mRNA was detected in most of endoneurial cells, which were further identified by immunocytochemistry as myelin 2', 3'-cyclic nucleotide 3'-phosphodiesterase containing Schwann cells. PC1 mRNA and protein were also present in cultured Schwann cells also containing convertases PC5, furin and PC7 as well as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Mostly unprocessed pro-NGF of 35 kDa and pro-BDNF of 35 kDa were found on Western blotting of Schwann cells. Expression of exogenous neurotrophins by infection with vaccinia virus vector showed that mouse pro-NGF and rat pro-BDNF are cleaved intracellularly on smaller forms of 13.5 kDa NGF and 14 kDa BDNF. Infection experiments demonstrated that Schwann cells contain active processing enzymes. In conclusion, this work provides in vivo evidence of the presence of several PCs in the injured rat sciatic nerve and ex vivo in cultured Schwann cells.
authors.affiliation: Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada. marcinm@ircm.umontreal.ca
authors.forename: M
authors.initials: M
authors.lastname: Marcinkiewicz
authors.forename: D
authors.initials: D
authors.lastname: Savaria
authors.forename: J
authors.initials: J
authors.lastname: Marcinkiewicz
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000235:genetics*; D015415:Biomarkers; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003714:Denervation; D045683:Furin; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D017403:In Situ Hybridization; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D045664:Proprotein Convertase 1; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000201:enzymology* / Q000821:virology; D012584:Sciatic Nerve / Q000737:chemistry / Q000601:surgery; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics*; D013381:Subtilisins / Q000032:analysis / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014615:Vaccinia
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D002273:Carcinogens; D007476:Ionophores; D009414:Nerve Growth Factors; D011498:Protein Precursors; D012333:RNA, Messenger; D005576:Colforsin; D015759:Ionomycin; C490930:Pcsk7 protein, mouse; C490931:Pcsk7 protein, rat; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C473807:propeptide convertase 5, rat; D045683:Furin; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1; D016282:Aspartic Acid Endopeptidases; D013755:Tetradecanoylphorbol Acetate