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Expression of ATP-binding cassette membrane transporters in a HIV-1 transgenic rat model.

Authors: Robillard, KR  Hoque, MT  Bendayan, R 
Citation: Robillard KR, etal., Biochem Biophys Res Commun. 2014 Feb 21;444(4):531-6. doi: 10.1016/j.bbrc.2014.01.092. Epub 2014 Jan 25.
Pubmed: (View Article at PubMed) PMID:24472536
DOI: Full-text: DOI:10.1016/j.bbrc.2014.01.092

P-glycoprotein (P-gp, product of Mdr1a and Mdr1b genes), multidrug resistance associated proteins (Mrps), and breast cancer resistance protein (Bcrp), all members of the ATP-binding cassette (ABC) membrane-associated drug transporters superfamily, can significantly restrict the entry of antiretroviral drugs (ARVs) into organs which exhibit a barrier function such as the central nervous system (CNS) and the male genital tract (MGT). In vitro, HIV-1 viral proteins such as glycoprotein-120 (gp120) and transcriptional transactivator (tat) have been shown to alter the expression of these transporters and ARVs permeability. The objective of this study was to compare mRNA expression of these transporters, in vivo, in several tissues obtained from HIV-1 transgenic rats (Tg-rat) (8 and 24 weeks) with those of age-matched wild-type rats. At 24 weeks, significant changes in several drug transporter mRNA expressions were observed, in particular, in brain, kidney, liver and testes. These findings suggest that HIV-1 viral proteins can alter the expression of ABC drug transporters, in vivo, in the context of HIV-1 and further regulate ARVs permeability in several organs including the CNS and MGT, two sites which have been reported to display very low ARVs permeability in the clinic.


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RGD Object Information
RGD ID: 11041168
Created: 2016-03-23
Species: All species
Last Modified: 2016-03-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.