Time-Dependent Lactate Production and Amino Acid Utilization in Cultured Astrocytes Under High Glucose Exposure

Time-Dependent Lactate Production and Amino Acid Utilization in Cultured Astrocytes Under High Glucose Exposure
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高葡萄糖暴露下培养的星形胶质细胞的时间依赖性乳酸产生和氨基酸利用

DOI:
10.1007/s12035-016-0360-y
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发表时间:
2017-01
期刊:
Mol Neurobiol
影响因子:
--
通讯作者:
Hongchang Gao
Hongchang Gao
中科院分区:
其他
文献类型:
--
作者:
Dan Wang;Liangcai Zhao;Hong Zheng;Minjian Dong;Linlin Pan;Xi Zhang;Huajie Zhang;Hongchang Gao

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累积的研究集中在糖尿病患者中枢神经系统(CNS)并发症的严重程度。高糖的作用可能与中枢神经系统代谢紊乱有关。星形胶质细胞具有强大的代谢调节能力,在中枢神经系统的生理和病理过程中起着重要作用。因此,深入分析星形胶质细胞暴露于HG的代谢变化将有助于探索潜在的发病机制。本研究采用基于1H NMR的代谢组学方法,以时间依赖的方式表征细胞内代谢物和相应培养基的代谢变化。我们的研究结果显示乳酸的产生和释放显着升高。亮氨酸、异亮氨酸、蛋氨酸和酪氨酸是最重要的代谢产物。此外,还观察到几种代谢途径的严重干扰,包括β-内酰胺酶调节、能量代谢和细胞生物合成。从这个意义上说,HG暴露下星形胶质细胞代谢的详细信息为我们提供了对高血糖或糖尿病期间中枢神经系统内在代谢障碍的全面了解。
Accumulating investigations have focused on the severity of central nervous system (CNS) complications in diabetic patients. The effects of the high glucose (HG) probably attribute to the metabolic disturbances in CNS. Astrocytes, with powerful ability of metabolic regulation, play crucial roles in physiological and pathological processes in CNS. Hence, an in-depth analysis as to metabolic alterations of astrocytes exposure to HG would facilitate to explore the underlying pathogenesis. In this study, the1H NMR-based metabonomic approach was performed to characterize the metabolic variations of intracellular metabolites and corresponding culture media in a time-dependent manner. Our results revealed a significant elevation in lactate production and release. Four amino acids, leucine, isoleucine, methionine and tyrosine, were the most important metabolites for utilization. Also, profound disturbances of several metabolic pathways, including osmoregulation, energy metabolism, and cellular biosynthesis were observed. In that sense, the detailed information of astrocyte metabolism under HG exposure provides us a comprehensive understanding of the intrinsic metabolic disorders in CNS during hyperglycemia or diabetes.
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