Kainic acid increases the expression of the prohormone convertases furin and PC1 in the mouse hippocampus.
Prohormone convertases (PCs) belong to the mammalian family of subtilisin/kexin-like enzymes which have been implicated in the posttranslational processing of precursor proteins. Several PCs are produced in the central and peripheral nervous system, and only a few specific precursor-substrates have been identified in vivo. In the nervous system, PCs may be involved in intracellular processing of precursors for neuropeptides, hormones and neurotrophic factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). To study the interrelationships between the convertases furin, PC1 and PC2, and the neurotrophins NGF, BDNF and NT-3, we compared their mRNA distribution in different tissues. We also examined their expression in the hippocampus of mice undergoing kainic acid-induced seizures. In this experiment, in situ hybridization (ISH) demonstrated that the levels of mRNA for furin, PC1 and BDNF increased maximally at 3 h after kainic acid administration, followed by a decline to normal levels by 96 h. NGF showed small changes, while NT-3 was downregulated with minimal expression levels between 3 to 12 h. Double ISH with radioactively-labeled riboprobes and digoxigenin-labeled riboprobes demonstrated colocalization of furin with NGF and BDNF in the mouse submaxillary gland, and of furin and PC1 with BDNF in the trigeminal ganglion. Based on colocalization studies and evidence of coordinate expression with NGF and BDNF, we suggest the involvement of furin in processing of proNGF, and of both furin and PC1 in processing of proBDNF.
J.A. DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada.
A
A
Meyer
P
P
Chrétien
G
G
Massicotte
C
C
Sargent
M
M
Chrétien
M
M
Marcinkiewicz
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D045683:Furin; D006624:Hippocampus / Q000201:enzymology*; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D020933:Neurotrophin 3; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000096:biosynthesis; D013363:Submandibular Gland / Q000201:enzymology; D013381:Subtilisins / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D012668:Trigeminal Ganglion / Q000201:enzymology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; D007608:Kainic Acid