ATP结合盒耐多药转运蛋白限制齐多夫定的抗艾滋病活动和indinavir感染人类的巨噬细胞。
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比结Jorajuria年代,Dereuddre-Bosquet N, F,马丁年代,Porcheray F, Garrigues, Mabondzo, Benech H,葛J, Orlowski年代,Dormont D, Clayette P
ATP结合盒耐多药转运蛋白限制齐多夫定的抗艾滋病活动和indinavir感染人类的巨噬细胞。
小红伞。2004年8月,9 (4):519 - 28。
- PubMed ID
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15456083 (在PubMed]
- 文摘
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目的:调查22 (P-gp)和多药耐药性是否蛋白质(可机读护照),而限制HIV蛋白酶抑制剂(pi)的生物利用度和核苷逆转录酶抑制剂(种转录),调节的抗艾滋病活动种转录,non-NRTIs和π体外。设计:我们使用的主要文化主要HIV靶细胞:人类monocyte-derived巨噬细胞和淋巴细胞(mdm)。方法:P-gp和MRP表达为了应对长期齐多夫定(3“-azido-3”脱氧胸苷;AZT)或indinavir治疗被rt - pcr量化。MDM和体外淋巴细胞被感染hiv - 1 / Ba-L和HIV-1-LAI,分别用抗逆转录病毒药物治疗。我们评估这些药物的活动结合PSC833, P-gp抑制剂,和/或丙磺舒,MRP1抑制剂。细胞内三磷酸AZT导数(AZT-TP)被HPLC-MSMS量化。P-gp atp酶活性测定P-gp由内而外原生膜囊泡丰富。结果:凋亡水平,mrp4 mrp5 mRNA和AZT治疗后高。在感染的MDM, PSC833和丙磺舒AZT和indinavir的抗艾滋病活动增加。 AZT (5 nM) decreased HIV replication by 34% alone and by 72% in combination with P-gp/MRP inhibitors. Indinavir (10 nM) gave 14% inhibition alone and 81% in combination. The increase in anti-HIV activity of AZT was correlated with an increase in intracellular AZT-TP concentration. However, unlike PIs, neither AZT nor its metabolites interacted with P-gp. CONCLUSION: AZT increases the expression of multidrug transporters, thereby decreasing its pharmacological activity. The cellular efflux of AZT probably involves MRP4 or MRP5. In contrast, increases in indinavir anti-HIV activity require the inhibition of both P-gp and MRP1.