Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells.
Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells.
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作者：
Amaral AI;Hadera MG;Tavares JM;Kotter MR;Sonnewald U
虽然少突胶质细胞在中枢神经系统（CNS）细胞中占很大比例，但对其中间代谢知之甚少。因此，我们利用同位素标记的代谢物表征了分化后期初代少突胶质前体细胞培养物的代谢功能。我们报道分化的少突胶质细胞系细胞在胞浆中代谢葡萄糖，在线粒体中代谢葡萄糖产生的丙酮酸。用[1,2‐13C]葡萄糖孵育后获得的代谢物标记模式表明，戊糖磷酸途径（PPP）在少突胶质细胞中高度活跃（磷酸烯醇丙酮酸的标记模式表明，大约10%的葡萄糖通过PPP代谢）。质谱分析和磁共振波谱分析分别用[1‐13C]乳酸或[1,2‐13C]葡萄糖培养细胞后的代谢物表明，被认为是星形胶质细胞专有的回旋丙酮酸羧化作用在少突胶质细胞中也很活跃。使用[1,2‐13C]醋酸，我们发现少突胶质细胞将醋酸转化为乙酰辅酶a，并在三羧酸循环中代谢。用[1,2‐13C]醋酸和[1,2‐13C]葡萄糖孵育细胞后，分析丙氨酸的标记模式显示苹果酸或草酰乙酸的分解代谢氧化。总之，我们报告了分化后期的少突胶质细胞谱系细胞是代谢高度活跃的细胞，可能对中枢神经系统的代谢活动有很大贡献。神经胶质2016;64:21-34
Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope‐labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2‐13C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1‐13C]lactate or [1,2‐13C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2‐13C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2‐13C]acetate and [1,2‐13C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS. GLIA 2016;64:21–34