scholarly journals Human–Mouse Chimeras with Normal Expression and Function Reveal That Major Domain Swapping Is Tolerated by P-Glycoprotein (ABCB1)

Biochemistry ◽  
2016 ◽  
Vol 55 (7) ◽  
pp. 1010-1023 ◽  
Author(s):  
Kristen M. Pluchino ◽  
Matthew D. Hall ◽  
Janna K. Moen ◽  
Eduardo E. Chufan ◽  
Patricia A. Fetsch ◽  
...  
Keyword(s):  
Domain Swapping ◽  
P Glycoprotein ◽  
Mouse Chimeras ◽  
Normal Expression ◽  
And Function ◽  
Major Domain

scholarly journals Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 834
Author(s):  
Anima M. Schäfer ◽  
Henriette E. Meyer zu Schwabedissen ◽  
Markus Grube
Keyword(s):  
Organic Anion ◽  
Physiological Role ◽  
Point Of View ◽  
Efflux Transporters ◽  
Organic Anion Transporting Polypeptides ◽  
Current State ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
And Function ◽  
Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

scholarly journals Stabilization, Characterization, and Selective Removal of Cystatin C Amyloid Oligomers

2013 ◽  
Vol 288 (23) ◽  
pp. 16438-16450 ◽  
Author(s):  
Gustav Östner ◽  
Veronica Lindström ◽  
Per Hjort Christensen ◽  
Maciej Kozak ◽  
Magnus Abrahamson ◽  
...  
Keyword(s):  
Cystatin C ◽  
Amyloid Fibrils ◽  
Dynamic Equilibrium ◽  
Biological Fluids ◽  
Polyacrylamide Gel Electrophoresis ◽  
Gel Filtration ◽  
Domain Swapping ◽  
Amyloid Angiopathy ◽  
Force Microscopy ◽  
And Function

The pathophysiological process in amyloid disorders usually involves the transformation of a functional monomeric protein via potentially toxic oligomers into amyloid fibrils. The structure and properties of the intermediary oligomers have been difficult to study due to their instability and dynamic equilibrium with smaller and larger species. In hereditary cystatin C amyloid angiopathy, a cystatin C variant is deposited in arterial walls and cause brain hemorrhage in young adults. In the present investigation, we use redox experiments of monomeric cystatin C, stabilized against domain swapping by an intramolecular disulfide bond, to generate stable oligomers (dimers, trimers, tetramers, decamers, and high molecular weight oligomers). These oligomers were characterized concerning size by gel filtration, polyacrylamide gel electrophoresis, and mass spectrometry, shape by electron and atomic force microscopy, and, function by assays of their capacity to inhibit proteases. The results showed the oligomers to be highly ordered, domain-swapped assemblies of cystatin C and that the oligomers could not build larger oligomers, or fibrils, without domain swapping. The stabilized oligomers were used to induce antibody formation in rabbits. After immunosorption, using immobilized monomeric cystatin C, and elution from columns with immobilized cystatin C oligomers, oligomer-specific antibodies were obtained. These could be used to selectively remove cystatin C dimers from biological fluids containing both dimers and monomers.

scholarly journals Effect of chronic renal failure on the expression and function of rat intestinal P‐glycoprotein in drug excretion

2001 ◽  
Vol 16 (8) ◽  
pp. 1607-1614 ◽  
Author(s):  
Céline Veau ◽  
Christine Leroy ◽  
Hélène Banide ◽  
Daniel Auchère ◽  
Sylviane Tardivel ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Drug Excretion ◽  
P Glycoprotein ◽  
And Function

scholarly journals P-glycoprotein expression and function in circulating blood cells from normal volunteers

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2451-2458 ◽  
Author(s):  
WT Klimecki ◽  
BW Futscher ◽  
TM Grogan ◽  
WS Dalton
Keyword(s):  
Nk Cell ◽  
Efflux Pump ◽  
Immunoblot Analysis ◽  
Rhodamine 123 ◽  
Double Labeling ◽  
Normal Volunteers ◽  
P Glycoprotein ◽  
Mdr1 Mrna ◽  
Mrna Analysis ◽  
And Function

Abstract In contrast to its clearly defined role as a multidrug efflux pump in neoplastic cells, the physiologic function of P-glycoprotein (P-gly) in normal cells is unclear. Recent reports identifying P-gly in normal blood and bone marrow suggest that hematopoietic development or function may be dependent on P-gly. To understand the normal function of P-gly in the blood, its level of expression and function must first be quantitated relative to a known standard. In this study, P-gly, MDR1 gene expression, and P-gly function were quantitated in normal leukocytes. P-gly and MDR1 expression were analyzed in individual leukocyte lineages (T-helper, T-suppressor, monocyte, granulocyte, B- lymphocyte, NK cell) from normal volunteers. P-gly on the cell surface was detected by fluorescent double-labeling for lineage (CD4, CD8, CD14, CD15, CD19, CD56, respectively) and P-gly (MRK16) with analysis by flow cytometry and in some cases immunoblot analysis. MDR1 mRNA analysis on purified lineages was performed using quantitative reverse transcription-polymerase chain reaction. P-gly function was determined for each lineage using dual-labeling for lineage and P-gly substrate (rhodamine 123). The P-gly expressing human myeloma cell line, 8226/Dox6, was used as a reference of comparison for levels of P-gly, MDR1 mRNA, and function. CD56+ cells expressed the highest levels of MDR1 mRNA followed by CD8+ > CD4+ approximately equal to CD15+ > CD19+ > CD14+, with percentage values relative to Dox6 of 49%, 17%, 8%, 8%, 4%, and 2%, respectively. The assays for P-gly immunofluorescence and function correlated well with mRNA analysis except for CD15+ cells (granulocytes), which showed a moderate MDR1 mRNA level with a lack of both function and surface P-gly staining. Granulocyte membranes did show P-gly on immunoblot analysis when probed with either C219 or JSB1. We conclude that (1) P-gly and the MDR1 mRNA are expressed in normal leukocytes, (2) this P-gly expression is lineage specific with relatively high levels among CD56+ cells, and (3) the expression of P- gly in granulocytes is not associated with transport of the P-gly substrate, rhodamine 123, out of the cell.

P-glycoprotein Expression, Localization, and Function in Sandwich-Cultured Primary Rat and Human Hepatocytes: Relevance to the Hepatobiliary Disposition of a Model Opioid Peptide

2004 ◽  
Vol 21 (7) ◽  
pp. 1294-1302 ◽  
Author(s):  
Keith A. Hoffmaster ◽  
Ryan Z. Turncliff ◽  
Edward L. LeCluyse ◽  
Richard B. Kim ◽  
Peter J. Meier ◽  
...  
Keyword(s):  
Opioid Peptide ◽  
Human Hepatocytes ◽  
P Glycoprotein ◽  
Hepatobiliary Disposition ◽  
And Function

scholarly journals Stimulation of P-Glycoprotein Expression and Function by KGF-2 Involves Both Transcriptional and Post-Translational Mechanisms

2011 ◽  
Vol 140 (5) ◽  
pp. S-659
Author(s):  
Seema Saksena ◽  
Shubha Priyamvada ◽  
Maria Akhter ◽  
Arivarasu Natarajan Anbazhagan ◽  
Anas Alakkam ◽  
...  
Keyword(s):  
P Glycoprotein ◽  
And Function ◽  
Translational Mechanisms ◽  
Stimulation Of
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