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

Robillard, Kevin R.; Hoque, Tozammel; Bendayan, Reina

doi:10.1016/j.bbrc.2014.01.092

Cited by 17 publications

(15 citation statements)

References 37 publications

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“…In addition, we detected gp120 in the CSF of both young and older animals with some Tg rats showing detectable levels of gp120 in their CSF but not in the serum or higher levels in the CSF than in the serum, suggesting local expression in the brain. This is further supported by the detection of mRNA expression of viral proteins in the brain lysates of the Tg animals, reproducing previous similar work (Peng, Vigorito, 2010, Robillard et al, 2014). In the Tg rat with continuous production of viral proteins since birth, the age of the animal would equate with time since infection in patients, further supporting the usefulness of the rat as a model of prolonged viral protein exposure.…”

Section: Discussionsupporting

confidence: 90%

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

Reid

Ibrahim

Kim

et al. 2016

Journal of Neuroimmunology

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The transgenic HIV-1 rat (Tg) is a commonly used neuroHIV model with documented neurologic/behavioral deficits. Using immunofluorescent staining of the Tg brain, we found astrocytic dysfunction/damage, as well as dopaminergic neuronal loss/dysfunction, both of which worsening significantly in the striatum with age. We saw mild microglial activation in young Tg brains, but this decreased with age. There were no differences in neurogenesis potential suggesting a neurodegenerative rather than a neurodevelopmental process. Gp120 CSF levels exceeded serum gp120 levels in some animals, suggesting local viral protein production in the brain. Further probing of the pathophysiology underlying astrocytic injury in this model is warranted.

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Section: Discussionsupporting

confidence: 90%

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

Reid

Ibrahim

Kim

et al. 2016

Journal of Neuroimmunology

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“…In this study, we have demonstrated a cell‐specific response of P‐glycoprotein and BCRP expression in response to HIV, which is consistent with recent findings of tissue‐specific differences in ABC transporter (P‐glycoprotein, Bcrp, Mrp1, Mrp4, Mrp5) expression within HIV transgenic rats [34]…”

Section: Discussionsupporting

confidence: 92%

The effects of human immunodeficiency virus infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model

Ellis

Marlin

Taylor

et al. 2014

Journal of Pharmacy and Pharmacology

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Objectives In HIV infection, decreased penetration of antiretroviral drugs is postulated to contribute to HIV persistence within lymphoid rich regions of the gastrointestinal (GI) tract. However, mechanistic explanations for this phenomenon remain unclear. Specifically, investigations of HIV effects on drug efflux proteins within intestinal models are minimal. Methods Using an in vitro co-culture model of the GI tract, effects of HIV infection on drug efflux proteins, P-glycoprotein and Breast Cancer Resistance Protein (BCRP) were evaluated. The influence of the HIV-1 protein, Tat, and oxidative stress on P-glycoprotein and BCRP also was evaluated. Key Findings P-glycoprotein expression demonstrated an HIV-induced upregulation in Caco-2 cells over time for cells grown in co-culture with resting lymphocytes. BCRP overall expression increased with HIV exposure in activated primary human lymphocytes co-cultured with Caco-2 cells. Tat treatment resulted in no significant alterations in P-glycoprotein (43% increase), BCRP expression, or oxidative stress. Conclusions HIV exposure within an in vitro intestinal model resulted in increases in, P-glycoprotein and BCRP in a cell specific manner. Additionally, observed changes were not mediated by Tat. Collectively, these results suggest that alterations in BCRP and P-glycoprotein may contribute, in part, to decreased antiretroviral concentrations within the gastrointestinal tract in HIV infection.

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“…Tissue inflammation and cytokine secretion are known to alter functional expression of drug transporters and CYP enzymes in other disease states (e.g., inflammatory bowel syndrome) (21). Furthermore, we and other investigators have previously reported that the functional expression of drug transporters in brain parenchyma, blood-brain and bloodtestis barriers, and sigmoid colon epithelium is altered by the HIV antigens, viral infection-associated inflammation, and ARVs (22)(23)(24)(25)(26)(27)(28). The main objective of this study was to investigate the impact of HIV-1 infection and suppressive ART on the expression of intestinal drug transporters and metabolic enzymes in the intestinal mucosa of HIV-infected subjects.…”

mentioning

confidence: 87%

HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition

Kis

Sankaran-Walters

Hoque

et al. 2016

Antimicrob Agents Chemother

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؉ ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV ؉ naive group than in the control group and was partially restored to baseline levels in HIV ؉ subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV ؉ subjects on ART relative to HIV ؉ ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV ؉ subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV ؉ subjects. This has clinical implications when using data from healthy volunteers to guide ART.

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

Cited by 17 publications

References 37 publications

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

The effects of human immunodeficiency virus infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model

HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition

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