Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells

International Journal of Molecular Sciences

Krzysztof Lewandowski¹  Marlena Zyśk²  Monika Sakowicz-Burkiewicz²  Tadeusz Pawełczyk²  Robert Kowalski³  Piotr Pikul³ 

[1]Clinical Laboratory University Clinical Center in Gdansk, 80-211 Gdansk, Poland

[2]Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland

[3]Laboratory of Molecular and Cellular Nephrology, Polish Academy of Science, 80-308 Gdansk, Poland

关键词: aspartate N-acetyltransferase;    streptozotocin;    SNAP;    primary neurons;    neural stem cells;    NAA;   

DOI  :  10.3390/ijms21228541

来源: DOAJ

【 摘 要 】

The N-acetylaspartate network begins in neurons with N-acetylaspartate production catalyzed by aspartate N-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in N-acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the N-acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25–75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/Nat8l mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the N-acetylaspartate network. This study shows that reduced N-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger N-acetylaspartate network fragility. To reveal why N-acetylaspartate is reduced in this pathology, other processes should be considered.

【 授权许可】

Unknown