Apolipoprotein E4 and A beta peptide 1-42 inhibit polyphosphoinositide biosynthesis in rat brain cortex.
Polyphosphoinositides synthesized by phosphatidylinositol 4-kinase, EC 2.7.1.67 (PI4K) and phosphatidylinositol 4-phosphate 5-kinase, EC 2.7.1.68 (PIP5K) are involved in cell signaling and cytoskeleton function. In this study, the effect of apolipoprotein E4 (apoE4) and amyloid beta peptide A beta 1-42 on PI4K and PIP5K activity in cortical synaptic plasma membranes from rat brain was investigated. The results indicated that 0.25 microM apoE4 inhibited PI4K and PIP5K by 40% and 30%, respectively, but 25 microM A beta 1-42 decreased exclusively PI4K activity by 20%. Although the mechanism of apoE4 and A beta action is unknown and needs future investigation, this study suggests that free radical-dependent protein oxidation may be involved in alteration of these enzymes.
Zambrzycka
Agata
A
Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, Pawińskiego 5, PL 02-106 Warsaw, Poland. agatazambrzycka@hotmail.com
Kacprzak
Maria
M
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000494:pharmacology* / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D018129:Phosphatidylinositol Phosphates; C075222:amyloid beta-protein (1-42); D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; C020077:1-phosphatidylinositol-4-phosphate 5-kinase