Possible link between glycolysis and apoptosis induced by sodium fluoride
Possible link between glycolysis and apoptosis induced by sodium fluoride
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DOI：
10.1177/154405910508401009
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发表时间：
2005-10-01
影响因子：
7.6
通讯作者：
Sakagami, H
中科院分区：
文献类型：
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作者：
Otsuki, S;Morshed, SRM;Sakagami, H
氟化物已被用于预防牙列中的龋齿，但这种化合物诱导细胞毒性的可能潜在机制仍不清楚。由于氟是已知的糖酵解酶的抑制剂，我们研究了氟化钠诱导的人早幼粒细胞白血病HL-60细胞凋亡和糖酵解之间的可能联系。NaF诱导的凋亡性细胞死亡的特征在于半胱天冬酶激活、核小体间DNA片段化、线粒体膜电位的丧失和凋亡小体的产生。与caspase-8相比，caspase-3和-9的活化更高，表明参与了外源性途径。葡萄糖的利用几乎被NaF停止，而谷氨酰胺的利用则被增强。NaF可促进Bad蛋白的表达，但对Bcl-2和Bax蛋白的表达无明显影响，并可降低HIF-1 α mRNA的表达。对这些数据的分析表明糖酵解和细胞凋亡之间可能存在联系。
Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1 alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.