High level of amyloid precursor protein expression in neurite-promoting olfactory ensheathing glia (OEG) and OEG-derived cell lines.
During all the life of a mammal, olfactory ensheathing glia (OEG) permit the entry and navigation of olfactory neuron axons from peripheral to central nervous system (CNS) territory. This physiological characteristic of OEG has been successfully used for promotion of axonal regeneration after CNS injury in animal models. However, cellular and molecular properties responsible for OEG regenerative ability remain to be unveiled. Two approaches may be followed: to carry out genomic or proteomic analysis to detect secreted and/or membrane bound molecules or to examine the expression of molecules previously described as neuritogenic. This is the case of amyloid precursor protein (APP), a neurite-promoting molecule. We have studied the expression of APP by OEG and OEG-derived clonal lines, immortalised with the large T antigen of SV40 (TEG lines). OEG express high levels of APP in vivo and in culture. TEG lines maintained high expression of APP. Western blot analysis showed the presence of high molecular weight forms of APP in OEG, corresponding probably to glycosylated forms and/or to higher expression of the full length APPs. The main APP isoforms present in OEG cultures were APP770 and 751. L-APP isoforms without the exon 15, which are those corresponding with proteoglycan forms, are predominant in glial cells. Our data showed that OEG had three times as much L-APP as astrocytes, which may correlate with OEG neuritogenic capacity. In conclusion APP, a neurite-promoting molecule, is produced by OEG. Its nexin activity, dependent on the Kunitz family of serine protease inhibitors (KPI) domain and/or in combination with its glycosylation level might contribute with other factors to the ability of these cells to foster axonal elongation.
Moreno-Flores
M Teresa
MT
Centro de Biología Molecular "Severo Ochoa", Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
Lim
Filip
F
Martín-Bermejo
M Jesús
MJ
Díaz-Nido
Javier
J
Avila
Jesús
J
Wandosell
Francisco
F
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D020033:Protein Isoforms; D012333:RNA, Messenger