Effects of aging and amyloid-beta peptides on choline acetyltransferase activity in rat brain.
Choline acetyltransferase (ChAT, acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), involved in the learning and memory processes is responsible for the synthesis of acetylcholine. There are many discrepancies in literature concerning ChAT activity during brain aging and the role of amyloid beta peptides in modulation of this enzyme. The aim of the study was to investigate the mechanism of ChAT regulation and age-related alteration of ChAT activity in different parts of the brain. Moreover the effect of Abeta peptides on ChAT activity in adult and aged brain was investigated. The enzyme activity was determined in the brain cortex, hippocampus and striatum in adult (4-months-old), adult-aged (14-months-old) and aged (24-months-old) animals. The highest ChAT activity was observed in the striatum. We found that inhibitors of protein kinase C, A, G and phosphatase A2 have no effect on ChAT activity and that this enzyme is not dependent on calcium ions. About 70% of the total ChAT activity is present in the cytosol. Arachidonic acid significantly inhibited cytosolic form of this enzyme. In the brain cortex and striatum from aged brain ChAT activity is inhibited by 50% and 37%, respectively. The aggregated form of Abeta 25-35 decreased significantly ChAT activity only in the aged striatum and exerted inhibitory effect on this enzyme in adult, however, statistically insignificant. ChAT activity in the striatum was diminished after exposure to 1 mM H2O2. The results from our study indicate that aging processes play a major role in inhibition of ChAT activity and that this enzyme in striatum is selectively sensitive for amyloid beta peptides.
Zambrzycka
Agata
A
Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warsaw.
Alberghina
Mario
M
Strosznajder
Joanna B
JB
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D002540:Cerebral Cortex / Q000201:enzymology / Q000254:growth & development; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003342:Corpus Striatum / Q000201:enzymology / Q000254:growth & development; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009928:Organ Specificity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D004492:Edetic Acid; D002795:Choline O-Acetyltransferase; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D002122:Calcium Chloride