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二甲基亚砜诱导HL60细胞向中性粒细胞分化过程中肌醇转运的变化

Changes in inositol transport during DMSO-induced differentiation of HL60 cells towards neutrophils.

作者信息

Baxter M A, Bunce C M, Lord J M, French P J, Michell R H, Brown G

机构信息

Department of Medicine, University of Birmingham, U.K.

出版信息

Biochim Biophys Acta. 1991 Jan 31;1091(2):158-64. doi: 10.1016/0167-4889(91)90056-4.

DOI:10.1016/0167-4889(91)90056-4
PMID:1995075
Abstract

[3H]Inositol uptake by HL60 cells was measured during DMSO-induced differentiation towards neutrophils. The values for Km (53.2 microM) and Vmax (5.3 pmol/min per 10(6) cells) obtained for control HL60 cells are in good agreement with previously published figures for this cell line. Inositol transport into HL60 cells was an active, saturable and specific process which was unaffected by extracellular glucose concentrations. Inositol transport rates changed during DMSO-induced differentiation of HL60 cells towards neutrophils. An increase in inositol transport rates occurred during the first 4 days of exposure to 0.9% DMSO and was concommitant with the period leading to growth arrest and prior to the acquisition of the differentiated phenotype. These changes preceded the rise in intracellular inositol concentration from 10.9 to 132.7 microM seen between day 1 and day 5. After 4 days exposure to DMSO the rate of inositol transport fell to a value of 3.2 +/- 0.3 pmol/min per 10(6) cells at day 7, this was accompanied by a small reduction in intracellular inositol from a peak value of 132.7 to 112 microM. The inositol transport rate, thus, appears to closely accompany changes in the intracellular concentration of inositol. Inositol transport in human peripheral blood neutrophils was an order of magnitude slower than the value for uninduced HL60 cells, but the Km for inositol transport was similar in both cell types and was unchanged during HL60 differentiation. This suggests that changes in inositol transport rate are achieved by the modulation of a commonly expressed inositol transporter, one consequence of which is the alteration of intracellular inositol concentrations.

摘要

在二甲基亚砜(DMSO)诱导HL60细胞向中性粒细胞分化的过程中,对[3H]肌醇摄取进行了测定。对照HL60细胞的米氏常数(Km,53.2微摩尔)和最大反应速度(Vmax,每10^6个细胞5.3皮摩尔/分钟)与该细胞系先前发表的数据高度一致。肌醇转运进入HL60细胞是一个主动、可饱和且特异的过程,不受细胞外葡萄糖浓度的影响。在DMSO诱导HL60细胞向中性粒细胞分化的过程中,肌醇转运速率发生了变化。在暴露于0.9% DMSO的前4天,肌醇转运速率增加,这与导致生长停滞并在获得分化表型之前的时期一致。这些变化先于第1天到第5天细胞内肌醇浓度从10.9微摩尔升至132.7微摩尔。暴露于DMSO 4天后,第7天肌醇转运速率降至每10^6个细胞3.2±0.3皮摩尔/分钟,同时细胞内肌醇从峰值132.7微摩尔略有下降至112微摩尔。因此,肌醇转运速率似乎与细胞内肌醇浓度的变化密切相关。人外周血中性粒细胞中的肌醇转运比未诱导的HL60细胞慢一个数量级,但两种细胞类型中肌醇转运的Km相似,且在HL60分化过程中不变。这表明肌醇转运速率的变化是通过调节一种普遍表达的肌醇转运体实现的,其结果之一是细胞内肌醇浓度的改变。

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