Human immunodeficiency virus I-induced expression of P-glycoprotein.
Human immunodeficiency virus I-induced expression of P-glycoprotein.
复制标题
人类免疫缺陷病毒 I 诱导的 P-糖蛋白表达。
DOI：
10.1016/0006-291x(90)90783-j
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发表时间：
1990
影响因子：
3.1
通讯作者：
Gupta,S
中科院分区：
文献类型：
--
作者：
Gollapudi,S;Gupta,S
由于3′-叠氮基-3 ′-脱氧胸苷（AZT）长期治疗HIV感染与体外抗AZT相关，我们研究了HIV是否可以诱导/扩增感染细胞中P-糖蛋白的表达，从而减少药物蓄积，导致对AZT的敏感性降低。我们发现，H9（T细胞系）和U937（单核细胞系）细胞，感染HIV后，表达的P-糖蛋白水平增加，积累显着减少AZT和柔红霉素相比，未感染的细胞。叠氮化钠增加了柔红霉素在感染细胞中的细胞内蓄积，提示了代谢活性药物外排机制。加入环孢菌素A部分纠正了HIV感染细胞中的细胞内药物蓄积。此外，与多药耐药肿瘤细胞相似，HIV感染的细胞显示质膜去极化。两者合计，这些数据表明，HIV诱导的P-糖蛋白表达增加可能是减少细胞内积累的抗病毒药和耐药性AZT和其他抗逆转录病毒药物的机制之一。
Because prolonged treatment of HIV infection with 3′-azido-3′-deoxythymidine (AZT) is associated within vitroresistance to AZT, we examined whether HIV could induce/amplify the expression of p-glycoprotein in infected cells resulting in reduced drug accumulation leading to reduced sensitivity to AZT. We show that both H9 (T cell line) and U937 (monocytic cell line) cells, upon infection with HIV, expressed increased levels of P-glycoprotein and accumulated significantly less AZT and daunorubicin as compared to uninfected cells. Sodium azide increased intracellular accumulation of daunorubicin in infected cells, suggesting a metabolically active drug efflux mechanism. Addition of cyclosporin A partially corrected intracellular drug accumulation in HIV infected cells. In addition, similar to multidrug resistant tumor cells, HIV-infected cells show depolarization of plasma membrane. Taken together, these data suggest that HIV-induced increased P-glycoprotein expression could be one of the mechanisms for reduced intracellular accumulation of antiviral agents and resistance to AZT and perhaps to other anti-retroviral agents.