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首页> 外文期刊>Journal of pharmaceutical sciences. >Enhancement of zidovudine transfer to molt-4 cells, a human t-cell model, by dehydroepiandrosterone sulfate.
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Enhancement of zidovudine transfer to molt-4 cells, a human t-cell model, by dehydroepiandrosterone sulfate.

机译:硫酸脱氢表雄酮可增强齐多夫定向人t细胞模型molt-4细胞的转移。

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A possible approach to improve antiretroviral therapy with nucleoside reverse transcriptase inhibitors is to enhance inhibitor delivery to CD4-positive T cells. We previously showed that dehydroepiandrosterone sulfate (DHEAS) enhances zidovudine (AZT) transfer into syncytiotrophoblast. Here, we investigated whether DHEAS also enhances AZT transfer into a cellular model of human T lymphocytes, and whether AZT is taken up by a specific transport system. The effects of DHEAS and related compounds on the uptake of [(3) H]AZT and other nucleosides by Molt-4 cells (a model of human CD4-positive T cells) were measured. [(3) H]AZT uptake by Molt-4 cells was nitrobenzylthioinosine insensitive and pH dependent, and the uptake was significantly inhibited by 1 mM ethylisopropylamiloride. [(3) H]AZT uptake by Molt-4 cells was increased in the presence of DHEAS, whereas uptake of other nucleosides was reduced. Kinetic study revealed that the maximum uptake velocity (up to 30 min) was increased in the presence of DHEAS. The structural requirements for AZT uptake-enhancing activity were studied using structural analogues of DHEAS. Estrone-3-sulfate and 16alpha-hydroxy DHEAS also enhanced AZT uptake into Molt-4 cells. The use of uptake enhancers may be a good strategy to improve the efficacy of antiretroviral therapy.
机译:用核苷逆转录酶抑制剂改善抗逆转录病毒疗法的一种可能方法是增强抑制剂向CD4阳性T细胞的递送。我们先前显示,硫酸脱氢表雄酮(DHEAS)增强齐多夫定(AZT)向合体滋养层细胞的转移。在这里,我们调查了DHEAS是否还增强了AZT转移到人T淋巴细胞的细胞模型中,以及AZT是否被特定的转运系统吸收。测量了DHEAS和相关化合物对Molt-4细胞(人CD4阳性T细胞的模型)对[(3)H] AZT和其他核苷摄取的影响。 [(3)H] AZT被Molt-4细胞摄取对硝基苄基硫代肌苷不敏感,并且依赖于pH,并且被1 mM乙基异丙基阿米洛利显着抑制。在DHEAS存在下,Molt-4细胞的[(3)H] AZT摄取增加,而其他核苷的摄取减少。动力学研究表明,在DHEAS存在下,最大摄取速度(长达30分钟)增加了。使用DHEAS的结构类似物研究了AZT摄取增强活性的结构要求。雌酮-3-硫酸盐和16α-羟基DHEAS还可增强AZT对Molt-4细胞的吸收。摄取促进剂的使用可能是提高抗逆转录病毒疗法疗效的好策略。

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