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Phosphoinositides kinases in brain aging and amyloid beta neurotoxicity
Author(s) -
Strosznajder J. B.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.85.s2.11_4.x
Subject(s) - phosphatidylinositol , kinase , phospholipase c , microbiology and biotechnology , phosphatidylinositol 4,5 bisphosphate , neurotoxicity , protein kinase c , chemistry , biochemistry , biology , signal transduction , organic chemistry , toxicity
Phosphatidylinositol 4‐kinase (PI‐4K) and phosphatidylinositol‐monophosphate 5‐kinase (PIP‐5K) are responsible for the synthesis of PIP and phosphatidylinositol‐(4,5)bisphosphate (PIP2) the substrates for phospholipase C (PLC). PIP2 is a preferential substrate for phosphatidylinositol‐3kinase (PI‐3K) regulator(s) of cytoskeleton function and cell survival. In this study modulation of phosphoinositides kinases by G protein, brain aging, amyloid beta (AB) 1‐42 and apolipoprotein E4 (ApoE4) was investigated. Our data indicate that aging affected phosphorylation of endogenous PIP but had no effect on PI‐4K and PIP‐5K in synaptic plasma membrane from brain cortex and hippocampus. AB 1‐42 and ApoE4 decrease by 50% PI‐4K and ApoE4 additionally inhibits PIP‐5K. The results with wortmanin suggest that AB 1‐42 and ApoE4 affected also PI‐3K. Our data indicate that AB peptides through arachidonic acid and free radicals decrease PI‐4K and PI‐3K activity and alter polyphosphoinositides synthesis and signaling.