Coapplication of Adenine with Inosine or Guanosine Supports Rapid ATP Restoration by ATP-deprived Cultured Primary Astrocytes

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gabriele Karger, Ralf Dringen
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引用次数: 0

Abstract

Astrocytes contain a high concentration of adenosine triphosphate (ATP) that enables these cells to perform their physiological functions in brain. To investigate the mechanisms involved in astrocytic ATP restoration, the ATP content of cultured primary rat astrocytes was first depleted by a preincubation with the mitochondrial uncoupler BAM15 before extracellular substrates and their combinations were applied to foster ATP restoration. To test for the contribution of the purine salvage pathway to synthesize new adenosine monophosphate (AMP) for ATP restoration, several purine nucleosides and purine bases as well as their combinations were applied. In the absence of glucose, partial ATP restoration was found for incubations with inosine and guanosine that was lowered by forodesine, an inhibitor of purine nucleoside phosphorylase. In glucose-fed cells, the coapplication of micromolar concentrations of adenine with inosine or guanosine, but not with ribose, accelerated ATP restoration in a concentration-dependent manner. By such treatments, 80% of the initial ATP content were restored within 40 min. The supporting effects of inosine and guanosine on ATP restoration were prevented by the presence of forodesine, demonstrating the contribution of purine nucleoside phosphorylase in the ATP restoration observed. These data demonstrate that ATP-deprived astrocytes need for rapid ATP restoration - in addition to glucose as energy substrate - an adenine source and inosine or guanosine as precursor for the ribose phosphate moiety of ATP.

腺嘌呤与肌苷或鸟苷的共应用支持ATP缺失培养的原代星形细胞快速恢复ATP
星形胶质细胞含有高浓度的三磷酸腺苷(ATP),使这些细胞能够在大脑中发挥其生理功能。为了研究星形胶质细胞ATP恢复的机制,首先用线粒体解耦剂BAM15预孵育培养的大鼠原代星形胶质细胞的ATP含量,然后用细胞外底物及其组合促进ATP恢复。为了测试嘌呤挽救途径在合成新的单磷酸腺苷(AMP)以恢复ATP中的作用,我们使用了几种嘌呤核苷和嘌呤碱基及其组合。在没有葡萄糖的情况下,发现与肌苷和鸟苷(嘌呤核苷磷酸化酶抑制剂)一起孵育的部分ATP恢复。在葡萄糖喂养的细胞中,微摩尔浓度的腺嘌呤与肌苷或鸟苷共施用,而不是与核糖共施用,以浓度依赖的方式加速ATP的恢复。经过这样的处理,在40分钟内恢复了80%的初始ATP含量。肌苷和鸟苷对ATP恢复的支持作用被福罗地碱的存在所阻止,这证明了嘌呤核苷磷酸化酶在ATP恢复中的作用。这些数据表明,缺乏ATP的星形胶质细胞需要快速的ATP恢复-除了葡萄糖作为能量底物-腺嘌呤来源和肌苷或鸟苷作为ATP核糖磷酸部分的前体。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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