Alteration in P-glycoprotein at the blood–brain barrier in the early period of MCAO in rats

Cen, Juan; Liu, Lu; Li, Mingshan; He, Ling; Lijuan, Wang; Liu, Yanqing; Liu, Meng; Ji, Bian‐Sheng

doi:10.1111/jphp.12033

Cited by 56 publications

(43 citation statements)

References 28 publications

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“…BBB P-gp expression and activity is elevated three hours following transient intraluminal middle cerebral artery occlusion (MCAO). The observed overexpression of P-gp was persistent up to 24 hours after reperfusion, independent of the severity of the ischaemic event and observed also in newly generated capillaries 14 days post-stroke (Cen et al, 2013; Dazert et al, 2006; Hermann et al, 2006; Ueno et al, 2009). In contrast only a few studies have investigated the role of other ABC efflux transporters at the BBB after brain ischaemia.…”

Section: Introductionmentioning

confidence: 73%

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

et al. 2015

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The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases.

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Section: Introductionmentioning

confidence: 73%

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

et al. 2015

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“…Cell lysate (80 μ g) was resolved on 4–12% SDS-PAGE gels and then transferred on to nitrocellulose membranes. The membranes were blocked with tris-buffered saline with 0.1% Tween 20 and 5% skim milk and then incubated with primary antibodies (1 : 100–1 : 5000) overnight at 4°C and then washed with TBST for three times and incubated with HRP-conjugated secondary antibody (1 : 2000) at room temperature for 1 h. Following three-time wash with TBST, the membranes were developed by the ECL detection kit [19]. The images of western blot were captured and analyzed by Bio-Rad imaging system.…”

Section: Methodsmentioning

confidence: 99%

Long‐Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF‐7 Cells

Cen

Zhang

Liu

et al. 2016

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) play an important role in multidrug resistance (MDR). This study aimed to investigate the effects of long-term ROS alteration on MDR in MCF-7 cells and to explore its underlying mechanism. Our study showed both long-term treatments of H2O2 and glutathione (GSH) led to MDR with suppressed iROS levels in MCF-7 cells. Moreover, the MDR cells induced by 0.1 μM H2O2 treatment for 20 weeks (MCF-7/ROS cells) had a higher viability and proliferative ability than the control MCF-7 cells. MCF-7/ROS cells also showed higher activity or content of intracellular antioxidants like glutathione peroxidase (GPx), GSH, superoxide dismutase (SOD), and catalase (CAT). Importantly, MCF-7/ROS cells were characterized by overexpression of MDR-related protein 1 (MRP1) and P-glycoprotein (P-gp), as well as their regulators NF-E2-related factor 2 (Nrf2), hypoxia-inducible factor 1 (HIF-1α), and the activation of PI3K/Akt pathway in upstream. Moreover, several typical MDR mediators, including glutathione S-transferase-π (GST-π) and c-Myc and Protein Kinase Cα (PKCα), were also found to be upregulated in MCF-7/ROS cells. Collectively, our results suggest that ROS may be critical in the generation of MDR, which may provide new insights into understanding of mechanisms of MDR.

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“…Because of the narrow therapeutic window for the stroke, it is crucial to investigate the changes in P‐gp expression at the BBB in the early period of the disease. Our previous report showed that increased P‐gp expression at the BBB and decreased concentration of rhodamine 123 (Rh123) and nimodipine in the ischeamic brain tissues were observed within 6 h and 4 h after middle cerebral artery occlusion in rats, respectively, accompanied with elevated tumour necrosis factor‐α (TNF‐α) and nitric oxide synthase (NOS) expression in brain microvessels . Accordingly, to investigate which factors are involved in the changes in P‐gp in the rBMECs during ischaemia may provide assistance for the modulation of the efflux pump.…”

Section: Introductionmentioning

confidence: 99%

Modulation of P-glycoprotein in rat brain microvessel endothelial cells under oxygen glucose deprivation

Cen

et al. 2013

Journal of Pharmacy and Pharmacology

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Alteration in P-glycoprotein at the blood–brain barrier in the early period of MCAO in rats

Abstract: P-gp plays a crucial role in limiting the entrance of agents into the brain after MCAO and the specific regulation of P-gp expression/activity may provide an important approach for the improvement of pharmacotherapy in ischaemic stroke.

Cited by 56 publications

References 28 publications

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

Long‐Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF‐7 Cells

Modulation of P-glycoprotein in rat brain microvessel endothelial cells under oxygen glucose deprivation

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