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Open AccessArticle

The Impact of Acetyl-CoA and Aspartate Shortages on the N-Acetylaspartate Level in Different Models of Cholinergic Neurons

Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland
Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Center, Polish Academy of Science, 80-308 Gdansk, Poland
Clinical Laboratory University Clinical Center in Gdansk, 80-211 Gdansk, Poland
Department of Laboratory Medicine, Medical University of Gdansk, 80-2011 Gdansk, Poland
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 522;
Received: 9 May 2020 / Revised: 3 June 2020 / Accepted: 11 June 2020 / Published: 13 June 2020
N-acetylaspartate is produced by neuronal aspartate N-acetyltransferase (NAT8L) from acetyl-CoA and aspartate. In cholinergic neurons, acetyl-CoA is also utilized in the mitochondrial tricarboxylic acid cycle and in acetylcholine production pathways. While aspartate has to be shared with the malate–aspartate shuttle, another mitochondrial machinery together with the tricarboxylic acid cycle supports the electron transport chain turnover. The main goal of this study was to establish the impact of toxic conditions on N-acetylaspartate production. SN56 cholinergic cells were exposed to either Zn2+ overload or Ca2+ homeostasis dysregulation and male adult Wistar rats’ brains were studied after 2 weeks of challenge with streptozotocin-induced hyperglycemia or daily theophylline treatment. Our results allow us to hypothesize that the cholinergic neurons from brain septum prioritized the acetylcholine over N-acetylaspartate production. This report provides the first direct evidence for Zn2+-dependent suppression of N-acetylaspartate synthesis leading to mitochondrial acetyl-CoA and aspartate shortages. Furthermore, Zn2+ is a direct concentration-dependent inhibitor of NAT8L activity, while Zn2+-triggered oxidative stress is unlikely to be significant in such suppression. View Full-Text
Keywords: 2-APB; zinc neurotoxicity; diabetes 2-APB; zinc neurotoxicity; diabetes
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Zyśk, M.; Sakowicz-Burkiewicz, M.; Pikul, P.; Kowalski, R.; Michno, A.; Pawełczyk, T. The Impact of Acetyl-CoA and Aspartate Shortages on the N-Acetylaspartate Level in Different Models of Cholinergic Neurons. Antioxidants 2020, 9, 522.

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