Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland.
Laboratory of Molecular and Cellular Nephrology, Polish Academy of Science, 80-308 Gdansk, Poland.
Int J Mol Sci. 2020 Nov 12;21(22):8541. doi: 10.3390/ijms21228541.
The -acetylaspartate network begins in neurons with -acetylaspartate production catalyzed by aspartate -acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in -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 -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/ 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 -acetylaspartate network. This study shows that reduced -acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger -acetylaspartate network fragility. To reveal why -acetylaspartate is reduced in this pathology, other processes should be considered.
乙酰天门冬氨酸网络始于神经元，其中乙酰天门冬氨酸由乙酰辅酶 A 和天门冬氨酸催化的天冬氨酸乙酰转移酶产生。临床研究报告称，1 型糖尿病患者大脑中的乙酰天门冬氨酸水平显著下降。本研究的主要目的是确定高血糖或氧化应激对乙酰天门冬氨酸网络的影响。在体外研究部分，胚胎大鼠原代神经元用一氧化氮发生器处理 24 小时，然后进行 6 天的后处理培养，而神经干细胞则在含有 25-75mM 葡萄糖的培养基中培养。在体内部分，雄性成年 Wistar 大鼠腹腔注射链脲佐菌素（65mg/kg 体重）诱导高血糖（糖尿病模型），并在 2 或 8 周后安乐死。最后，分析了生化特征、NAT8L 蛋白/ mRNA 水平和酶活性。持续的氧化应激过程显著影响能量代谢和胆碱能神经传递。然而，应用的因素并没有影响乙酰天门冬氨酸网络。本研究表明，1 型糖尿病中乙酰天门冬氨酸水平降低与氧化应激无关，也不会引发乙酰天门冬氨酸网络脆弱性。为了揭示为什么在这种病理中乙酰天门冬氨酸减少，应该考虑其他过程。
