期刊
ACS CHEMICAL NEUROSCIENCE
卷 11, 期 17, 页码 2717-2727出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00353
关键词
acidosis; cell vulnerability; lactate flux; monocarboxylate transporter 1; oligodendrocyte precursor cells
资金
- Hudson Team grant from ALS Canada
- Brain Canada
- Guangdong Innovation grant [2015KGJH018]
- Shantou University
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.
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