Kowalski Robert, Pikul Piotr, Lewandowski Krzysztof, Sakowicz-Burkiewicz Monika, Pawełczyk Tadeusz, Zyśk Marlena
University Clinical Center in Gdansk, 80-952 Gdansk, Poland.
Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 80-308 Gdansk, Poland.
Antioxidants (Basel). 2021 Sep 1;10(9):1404. doi: 10.3390/antiox10091404.
Neuronal -acetylaspartate production appears in the presence of aspartate -acetyltransferase (NAT8L) and binds acetyl groups from acetyl-CoA with aspartic acid. Further -acetylaspartate pathways are still being elucidated, although they seem to involve neuron-glia crosstalk. Together with -acetylaspartate, NAT8L takes part in oligoglia and astroglia cell maturation, myelin production, and dopamine-dependent brain signaling. Therefore, understanding -acetylaspartate metabolism is an emergent task in neurobiology. This project used in in vitro and in vivo approaches in order to establish the impact of maturation factors and glial cells on -acetylaspartate metabolism. Embryonic rat neural stem cells and primary neurons were maturated with either nerve growth factor, -retinoic acid or activators of cAMP-dependent protein kinase A (dibutyryl-cAMP, forskolin, theophylline). For in vivo, adult male Wistar rats were injected with theophylline (20 mg/kg b.w.) daily for two or eight weeks. Our studies showed that the -acetylaspartate metabolism differs between primary neurons and neural stem cell cultures. The presence of glia cells protected -acetylaspartate metabolism from dramatic changes within the maturation processes, which was impossible in the case of pure primary neuron cultures. In the case of differentiation processes, our data points to dibutyryl-cAMP as the most prominent regulator of -acetylaspartate metabolism.
神经元 - 乙酰天冬氨酸的产生出现在天冬氨酸 - 乙酰转移酶（NAT8L）存在的情况下，它将乙酰辅酶A中的乙酰基团与天冬氨酸结合。尽管其进一步的代谢途径似乎涉及神经元 - 神经胶质细胞间的相互作用，但仍在研究之中。NAT8L与 - 乙酰天冬氨酸一起参与少突胶质细胞和星形胶质细胞的成熟、髓磷脂的产生以及多巴胺依赖的脑信号传导。因此，了解 - 乙酰天冬氨酸的代谢是神经生物学中的一项紧迫任务。本项目采用体外和体内方法，以确定成熟因子和神经胶质细胞对 - 乙酰天冬氨酸代谢的影响。用神经生长因子、 - 视黄酸或环磷酸腺苷依赖性蛋白激酶A的激活剂（二丁酰环磷腺苷、福斯可林、茶碱）使胚胎大鼠神经干细胞和原代神经元成熟。在体内实验中，成年雄性Wistar大鼠每天注射茶碱（20毫克/千克体重），持续两周或八周。我们的研究表明，原代神经元和神经干细胞培养物中的 - 乙酰天冬氨酸代谢有所不同。神经胶质细胞的存在保护了 - 乙酰天冬氨酸代谢在成熟过程中不发生剧烈变化，而在纯原代神经元培养物中则无法做到这一点。在分化过程中，我们的数据表明二丁酰环磷腺苷是 - 乙酰天冬氨酸代谢最主要的调节因子。
