Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.
Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.
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DOI：
10.1002/jcp.25690
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发表时间：
2017-05
影响因子：
5.6
通讯作者：
Ogata T
中科院分区：
文献类型：
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作者：
Ichihara Y;Doi T;Ryu Y;Nagao M;Sawada Y;Ogata T
少突胶质细胞祖细胞（oligodendrocytes progenitor cells, OPCs）经过显著的形态学变化成为成熟的少突胶质细胞，但这一过程的代谢资源尚未完全阐明。尽管有报道称，糖原的代谢衍生物乳酸作为代谢物在少突胶质细胞中被消耗，并改善低糖条件下诱导的低髓鞘形成，但乳酸对OPCs细胞循环和分化的直接作用以及乳酸的来源尚不清楚。因此，我们评估了1,4‐二脱氧‐1,4‐亚氨基‐d‐阿拉伯糖醇（DAB）在小鼠铜酮模型中的作用，DAB是糖原分解代谢酶糖原磷酸化酶的抑制剂。铜酮诱导胼胝体脱髓鞘，并在铜酮停止治疗后发生再脱髓鞘。DAB可抑制这种髓鞘再生。为了进一步研究乳酸是否影响OPC的增殖或分化，我们培养了小鼠原代富含OPC的细胞，并分析了乳酸的作用。通过BrdU阳性细胞比例评估，乳酸可挽救0.4 mM葡萄糖诱导的细胞周期减慢。通过监测成熟少突胶质细胞标志物髓鞘碱性蛋白，乳酸也促进OPC分化，在36.6 mM和0.4 mM葡萄糖的存在下。此外，这些乳酸介导的效应被报道的单羧酸转运蛋白抑制剂α‐氰基‐4‐羟基‐肉桂酸抑制。这些结果表明，乳酸直接促进了OPCs的细胞循环速率和分化，而糖原作为乳酸的来源之一，在体内有助于髓鞘再生。j .细胞。中国生物医学工程学报，2016,32(2):387 - 398。©2016作者。细胞生理学杂志，Wiley期刊公司出版。
Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4‐dideoxy‐1,4‐imino‐d‐arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC‐rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU‐positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate‐mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α‐cyano‐4‐hydroxy‐cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986–995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.