Compromised Lactate Efflux Renders Vulnerability of Oligodendrocyte Precursor Cells to Metabolic Stresses.,ACS Chemical Neuroscience

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Compromised Lactate Efflux Renders Vulnerability of Oligodendrocyte Precursor Cells to Metabolic Stresses.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-07-15 , DOI: 10.1021/acschemneuro.0c00353
Nan Zhang _{1,

2,

3} , Teng Guan ₂ , Kashfia Shafiq ₂ , Yuan Xing ₃ , Baoliang Sun ₄ , Qingjun Huang ₁ , Jiming Kong _{1,

2}

Affiliation

Among the brain cells, oligodendrocyte progenitor cells (OPCs) are the most vulnerable in response to hypoxic and ischemic insults, of which the mechanism remains unknown. Brain cells are known to import or export lactate via differentially expressed monocarboxylate transporters (MCTs) to maintain energy metabolism and pH homeostasis. The present study aims to determine the role of MCT1 in the high vulnerability of OPCs. Here we show that a mild ischemic condition equivalent to ischemic preconditioning caused detectable loss of OPCs. MCT1, which is primarily expressed in oligodendrocyte lineage cells including OPCs, was up-regulated immediately under oxygen–glucose deprivation (OGD) conditions. However, persistent hypoxia, but not hypoglycemia, inhibited the function of MCT1, leading to an intracellular lactate accumulation and acidosis in OPCs. Neurons, which express primarily MCT2, were able to export lactate and maintain an intracellular pH homeostasis under similar conditions. The results support that compromised lactate efflux resulting from hypoxia-induced dysfunction of MCT1 contributes to the high vulnerability of OPCs.

中文翻译：

妥协的乳酸外流使少突胶质前体细胞易受代谢应激的影响。

在脑细胞中，少突胶质细胞祖细胞（OPCs）最容易受到缺氧和缺血性损伤的影响，其机制尚不清楚。已知脑细胞通过差异表达的单羧酸盐转运蛋白（MCT）进口或出口乳酸，以维持能量代谢和pH稳态。本研究旨在确定MCT1在OPC的高度脆弱性中的作用。在这里，我们显示了与缺血预处理等效的轻度缺血状态导致可检测到的OPC丢失。MCT1主要在包括OPC在内的少突胶质细胞谱系细胞中表达，在缺氧-葡萄糖剥夺（OGD）条件下立即上调。但是，持续的低氧而不是低血糖抑制了MCT1的功能，导致OPC中的细胞内乳酸积累和酸中毒。主要表达MCT2的神经元能够在相似条件下输出乳酸并维持细胞内pH稳态。结果支持由缺氧诱导的MCT1功能障碍导致的乳酸外流受损导致OPC的高度脆弱性。

更新日期：2020-09-02

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