Understanding the function of the membrane transporter ABCG2 by comparison with-P glycoprotein: interaction with antitumorals, antibiotics, hormones and other compounds = Estudio de la función del transportador de membrana ABCG2 mediante comparación con la glicoproteína-P: interacción con antitumorales, antibióticos, hormonas y otros compuestos

2014 ◽  
Author(s):  
Estefanía Egido de Frutos
Keyword(s):  
Membrane Transporter ◽  
P Glycoprotein

scholarly journals Transport of Alzheimer’s associated amyloid-β catalyzed by P-glycoprotein

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250371
Author(s):  
James W. McCormick ◽  
Lauren Ammerman ◽  
Gang Chen ◽  
Pia D. Vogel ◽  
John G. Wise
Keyword(s):  
Cell Culture ◽  
Atp Hydrolysis ◽  
Amyloid Β ◽  
Md Simulations ◽  
Membrane Transporter ◽  
Biochemical Activity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Hydrolysis Activity

P-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and is implicated in Alzheimer’s disease (AD). However, previous studies on the ability of P-gp to directly transport the Alzheimer’s associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, transport substrate accumulation studies in cell culture, and biochemical activity assays to show that P-gp actively transports Aβ. We observed transport of Aβ40 and Aβ42 monomers by P-gp in explicit MD simulations of a putative catalytic cycle. In in vitro assays with P-gp overexpressing cells, we observed enhanced accumulation of fluorescently labeled Aβ42 in the presence of Tariquidar, a potent P-gp inhibitor. We also showed that Aβ42 stimulated the ATP hydrolysis activity of isolated P-gp in nanodiscs. Our findings expand the substrate profile of P-gp, and suggest that P-gp may contribute to the onset and progression of AD.

scholarly journals Transport of Alzheimer’s Associated Amyloid-β Catalyzed by P-glycoprotein

2020 ◽  
Author(s):  
James W. McCormick ◽  
Lauren Ammerman ◽  
Gang Chen (党陈) ◽  
Pia D. Vogel ◽  
John G. Wise
Keyword(s):  
Cell Culture ◽  
Atp Hydrolysis ◽  
Amyloid Β ◽  
Md Simulations ◽  
Membrane Transporter ◽  
Biochemical Activity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Hydrolysis Activity

ABSTRACTP-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and is implicated in Alzheimer’s disease (AD). However, previous studies on the ability of P-gp to directly transport the Alzheimer’s associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, transport substrate accumulation studies in cell culture, and biochemical activity assays to show that P-gp actively transports Aβ. We observed transport of Aβ40 and Aβ42 monomers by P-gp in explicit MD simulations of a putative catalytic cycle. In in vitro assays with P-gp overexpressing cells, we observed enhanced accumulation of fluorescently labeled Aβ42 in the presence of Tariquidar, a potent P-gp inhibitor. We also showed that Aβ42 stimulated the ATP hydrolysis activity of isolated P-gp in nanodiscs. Our findings expand the substrate profile of P-gp, and suggest that P-gp may contribute to the onset and progression of AD.

scholarly journals P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy

2018 ◽  
Vol 26 (4) ◽  
pp. 466-473 ◽  
Author(s):  
Natalia M. Popova ◽  
Aleksey V. Shchulkin ◽  
Ivan V. Chernykh ◽  
Anna S. Esenina ◽  
Maria M. Gradinar ◽  
...  
Keyword(s):  
Functional Activity ◽  
Pharmacokinetic Parameters ◽  
Membrane Transporter ◽  
Serum Concentrations ◽  
Transporter Protein ◽  
The Third ◽  
P Glycoprotein ◽  
Reliable Increase ◽  
Abcb1 Protein

P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter protein that plays the key role in pharmacokinetics of drugs with a broad spectrum of action. Substrates of this transporter are some medical drugs (antibacterial, antiretroviral, hypotensive) that are prescribed to pregnant women for long-term intake, sometimes throughout the whole gestation period. Aim to study the activity of Pgp on the organism level in rabbits of Soviet Chinchilla breed in pregnancy. Materials and Methods. The study was performed on 21 Soviet Chinchilla female rabbits (3000-3500 g). The animals were divided into 3 series. The first series (n=6) included rabbits with 7 days of pregnancy; the second series (n=5) - animals with 14 days of pregnancy; the third series (n=10) - rabbits with 21 days of pregnancy. 7 Days before the study and in the indicated gestation periods, functional activity of Pgp was assessed by the pharmacokinetics of marker transporter substrate – fexofenadine, after its single oral introduction (67.5 mg/kg). Besides, serum concentrations of progesterone, estradiol, testosterone and prolactin were determined by radio immune method Results. In all the studied gestational periods, serum concentrations of estradiol, testosterone and prolactin did not significantly differ from those before pregnancy, but the level of progesterone in blood serum was significantly elevated above the norm. On the 7th day of pregnancy pharmacokinetic parameters of fexofenadine did not show any reliable changes as compared to the initial va-lues. On the 14th day of pregnancy a reliable increase in Cmax, AUC0-t, T1/2 of fexofenadine was noted as compared to the parameters before pregnancy, which indicates a decrease in Pgp functional activity on the organism level. On the 21st day of pregnancy Cmax of fexofenadine remained elevated. Other pharmacokinetic parameters of fexofenadine did not show reliable changes. Conclusion. Reduction in Pgp functional activity, determined by the pharmacokinetics of its marker substrate (fexofenadine), was noted in rabbits of Soviet Chinchilla breed on the 14th and 21st days of pregnancy with the underlying significant increase in progesterone level.

Pharmacogenetics of Clozapine: In Vivo Role of Cytochrome P450 Isoforms and P-Glycoprotein

2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap
Keyword(s):  
Cytochrome P450 ◽  
P Glycoprotein ◽  
Cytochrome P450 Isoforms
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