Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons

Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other ce...

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Veröffentlicht in:Journal of Neural Transmission 2000-01, Vol.107 (4), p.451-461
Hauptverfasser: HOLZER, M, BRÜCKNER, M. K, BECK, M, BIGL, V, ARENDT, T
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container_end_page 461
container_issue 4
container_start_page 451
container_title Journal of Neural Transmission
container_volume 107
creator HOLZER, M
BRÜCKNER, M. K
BECK, M
BIGL, V
ARENDT, T
description Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.
doi_str_mv 10.1007/s007020070087
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subjects Amyloid beta-Peptides - drug effects
Amyloid beta-Peptides - secretion
Amyloid beta-Protein Precursor - drug effects
Amyloid beta-Protein Precursor - secretion
Animals
Biological and medical sciences
Brain
Cells, Cultured
DNA Fragmentation - drug effects
DNA Fragmentation - physiology
Embryo, Mammalian
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Guinea Pigs
Isolated neuron and nerve. Neuroglia
Mitogen-Activated Protein Kinases - drug effects
Mitogen-Activated Protein Kinases - metabolism
Neurons - drug effects
Neurons - secretion
Okadaic Acid - pharmacology
Phosphorylation
Vertebrates: nervous system and sense organs
title Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons
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