Acetyl-CoA metabolism in cholinergic neurons and their susceptibility to neurotoxic inputs.
Cholinergic neurons, unlike other brain cells utilize acetyl-CoA not only for energy production but also for acetylcholine (ACh) synthesis. Therefore, suppression of acetyl-CoA metabolism by different neurotoxic inputs may be particularly harmful for this group of cells. Differentiation of SN56 cholinergic hybrid cells increased their choline acetyltransferase (ChAT) activity and ACh content but depressed pyruvate dehydrogenase activity and acetyl-CoA content. Differentiated cells were more susceptible to acute and chronic influences of aluminum, NO and amyloid-beta. Al decreased acetyl-CoA content, ACh release and increased Ca accumulation in differentiated cells (DC) to much higher degree than in non-differentiated ones (NC). NO strongly depressed acetyl-CoA level and increased ACh release in DC but did not affect NC. Additive effects of Al and NO were seen in DC but not in NC. Also long term suppressory effects of amyloid-beta, Al and NO on cholinergic phenotype and morphologic maturation were more evident in DC than in NC. Thus, relative shortage of acetyl-CoA in highly differentiated cholinergic neurons could make them particularly susceptible to degenerative insults in the course of different cholinergic encephalopathies.
Szutowicz
A
A
Department of Clinical Biochemistry, Medical University of Gdansk, Poland. aszut@amedec.amg.gda.pl
Tomaszewicz
M
M
Jankowska
A
A
Madziar
B
B
Bielarczyk
H
H
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000109:Acetylcholine / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004351:Drug Resistance; D006822:Hybrid Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D020030:Nitric Oxide Donors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D009599:Nitroprusside; D009569:Nitric Oxide; D000105:Acetyl Coenzyme A; D000535:Aluminum; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine