Gondáš Eduard, Baranovičová Eva, Šofranko Jakub, Murín Radovan
Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovakia.
Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovakia.
Biomedicines. 2024 Aug 8;12(8):1803. doi: 10.3390/biomedicines12081803.
Astrocytes are considered to possess a noticeable role in brain metabolism and, as a partners in neuron-glia cooperation, to contribute to the synthesis, bioconversion, and regulation of the flux of substrates for neuronal metabolism. With the aim of investigating to what extent human astrocytes are metabolizing amino acids and by which compounds are they enriching their surroundings, we employed a metabolomics analysis of their culture media by H-NMR. In addition, we compared the composition of media with either 5 mM or 25 mM glucose. The quantitative analysis of culture media by H-NMR revealed that astrocytes readily dispose from their milieu glutamine, branched-chain amino acids, and pyruvate with significantly high rates, while they enrich the culture media with lactate, branched-chain keto acids, citrate, acetate, ketone bodies, and alanine. Hyperglycemia suppressed the capacity of astrocytes to release branched-chain 2-oxo acids, while stimulating the generation of ketone bodies. Our results highlight the active involvement of astrocytes in the metabolism of several amino acids and the regulation of key metabolic intermediates. The observed metabolic activities of astrocytes provide valuable insights into their roles in supporting neuronal function, brain metabolism, and intercellular metabolic interactions within the brain. Understanding the complex metabolic interactions between astrocytes and neurons is essential for elucidating brain homeostasis and the pathophysiology of neurological disorders. The observed metabolic activities of astrocytes provide hints about their putative metabolic roles in brain metabolism.
星形胶质细胞被认为在脑代谢中发挥着显著作用，并且作为神经元 - 胶质细胞合作的伙伴，有助于神经元代谢底物的合成、生物转化和通量调节。为了研究人类星形胶质细胞在何种程度上代谢氨基酸以及它们通过哪些化合物丰富其周围环境，我们采用核磁共振氢谱（H-NMR）对其培养基进行代谢组学分析。此外，我们比较了含有5 mM或25 mM葡萄糖的培养基的成分。通过H-NMR对培养基进行定量分析表明，星形胶质细胞能够以显著高的速率从其周围环境中清除谷氨酰胺、支链氨基酸和丙酮酸，同时它们使培养基中富含乳酸、支链酮酸、柠檬酸、乙酸、酮体和丙氨酸。高血糖抑制了星形胶质细胞释放支链2-氧代酸的能力，同时刺激了酮体的生成。我们的结果突出了星形胶质细胞在几种氨基酸代谢以及关键代谢中间体调节中的积极参与。观察到的星形胶质细胞的代谢活动为其在支持神经元功能、脑代谢和脑内细胞间代谢相互作用中的作用提供了有价值的见解。了解星形胶质细胞与神经元之间复杂的代谢相互作用对于阐明脑内稳态和神经疾病的病理生理学至关重要。观察到的星形胶质细胞的代谢活动为其在脑代谢中假定的代谢作用提供了线索。
