L-glutamate and phorbol ester stimulate the release of secretory amyloid precursor protein from rat cortical synaptosomes.
Treatment of rat cortical synaptosomes with micromolar concentrations of L-glutamate stimulated the release of the secreted form of amyloid precursor protein in a concentration-dependent, however biphasic manner as assayed by semiquantitative Western blot analysis. The secreted amyloid precursor protein released from synaptosomes into the incubation medium was highest in the presence of 500 microM L-glutamate (about 64% over the level assayed in the incubation medium in the absence of any drug). In contrast, direct stimulation of protein kinase C by phorbol-12-myristate-13-acetate resulted in a concentration-independent increase in secretory amyloid precursor protein release by about 100% already detectable at a concentration of 0.1 microM but with no significant change at higher concentrations up to 10 microM. The presented data show that there is a constitutive release of secretory amyloid precursor protein from synaptosomes and suggest that (i) processing of amyloid precursor protein at the synaptic level is controlled by L-glutamate presumably via activation of protein kinase C, and (ii) isolated cortical synaptosomes represent a useful experimental approach to selectively study amyloid precursor protein metabolism at the synaptic level.
Kirazov
L
L
Department of Neuromorphology, Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 25, 1113 Sofia, Bulgaria. lkirazov@yahoo.com
Kirazovi
E
E
Schliebs
R
R
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate