The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis

2006 ◽  
Vol 9 (4-5) ◽  
pp. 227-246 ◽  
Author(s):  
Yehuda G. Assaraf
Keyword(s):  
Multidrug Resistance ◽  
Efflux Transporters ◽  
Folate Homeostasis ◽  
Antifolate Resistance

The role of multidrug resistance proteins MRP1, MRP2 and MRP3 in cellular folate homeostasis

2003 ◽  
Vol 65 (5) ◽  
pp. 765-771 ◽  
Author(s):  
Jan Hendrik Hooijberg ◽  
Godefridus J. Peters ◽  
Yehuda G. Assaraf ◽  
Ietje Kathmann ◽  
David G. Priest ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Folate Homeostasis

The function of multidrug resistance-associated protein 3 in the transport of bile acids under normal physiological and lithocholic acid-induced cholestasis conditions

2021 ◽  
Vol 22 ◽  
Author(s):  
Wenyu Wang ◽  
Sijing Zeng ◽  
Ming Hu ◽  
Zhongqiu Liu ◽  
Lingzhi Gong
Keyword(s):  
Multidrug Resistance ◽  
Bile Acid ◽  
Bile Acids ◽  
Physiological Condition ◽  
Lithocholic Acid ◽  
Efflux Transporters ◽  
Valuable Insight ◽  
Wild Type ◽  
Normal Physiological Condition

Background: The role of multidrug resistance-associated protein 3 (Mrp3) in the transport of bile acid (BA) in drug-induced cholestasis have not been well studied. Objective: In this study, wild type and Mrp3 knockout (Mrp3-/- ) mice under normal physiological and lithocholic acid (LCA)-induced cholestatic conditions were employed to investigate the role of Mrp3 in BA transport. Method: The levels of BA in serum, liver, gallbladder, intestine, kidney, feces and urine were quantified in both wild type and Mrp3-/- mice via ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS). Quantitative real time PCR (RT-PCR) analysis was used to measure the expression of genes related to the transport and synthesis of BA. Results: The results showed that the liver did not suffer more serious damage as a result of cholestasis when Mrp3 was depleted. The level of some individual bile acids changed apparently in the compartments of enterohepatic circulation (EHC) between the two control and model groups, respectively, but the level of serum total bile acid was only slightly reduced for Mrp3-/- groups. In addition, the level of BA-related efflux transporters and synthases increased significantly when Mrp3 was knocked out under normal physiological condition, but negligible alteration of them appeared under cholestatic condition. Conclusion: Our results indicated that Mrp3 could be responsible for the transport of some specific bile acids, and part of the Mrp3 role could be compensated for by other transporters. Moreover, Mrp3 deficiency has a direct effect on the expression of BA-related synthases and efflux transporters under normal physiological condition, but this effect could be less prominent under cholestatic condition. This study could provide much valuable insight into the physiological function of Mrp3 in the transport of bile acids.

Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy

2018 ◽  
Vol 17 (10) ◽  
pp. 728-735 ◽  
Author(s):  
Xiaolin Deng ◽  
Yangmei Xie ◽  
Yinghui Chen
Keyword(s):  
Antiepileptic Drugs ◽  
Abc Transporters ◽  
Refractory Epilepsy ◽  
Vascular Endothelial Cells ◽  
Efflux Transporters ◽  
Vascular Endothelial ◽  
Intracellular Signalling Pathways ◽  
The Brain ◽  
Transporter Expression

Background & Objective: Epilepsy is a common and serious chronic neurological disorder that is mainly treated with antiepileptic drugs. Although current antiepileptic drugs used in clinical practice have advanced to the third generation, approximately one-third of patients are refractory to these treatments. More efficacious treatments for refractory epilepsy are therefore needed. A better understanding of the mechanism underlying refractory epilepsy is likely to facilitate the development of a more effective therapy. The abnormal expression and/or dysfunction of efflux transporters, particularly ABC transporters, might contribute to certain cases of refractory epilepsy. Inflammation in the brain has recently been shown to regulate the expression and/or function of ABC transporters in the cerebral vascular endothelial cells and glia of the blood-brain barrier by activating intracellular signalling pathways. Conclusion: Therefore, in this review, we will briefly summarize recent research advances regarding the possible role of neuroinflammation in regulating ABC transporter expression in epilepsy.

scholarly journals Fructose Induces Fluconazole Resistance in Candida albicans through Activation of Mdr1 and Cdr1 Transporters

2021 ◽  
Vol 22 (4) ◽  
pp. 2127
Author(s):  
Jakub Suchodolski ◽  
Anna Krasowska
Keyword(s):  
Candida Albicans ◽  
Multidrug Resistance ◽  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
De Novo ◽  
Pathogenic Fungus ◽  
Serum Levels ◽  
Efflux Transporters ◽  
Fluconazole Resistance ◽  
Green Fluorescent

Candida albicans is a pathogenic fungus that is increasingly developing multidrug resistance (MDR), including resistance to azole drugs such as fluconazole (FLC). This is partially a result of the increased synthesis of membrane efflux transporters Cdr1p, Cdr2p, and Mdr1p. Although all these proteins can export FLC, only Cdr1p is expressed constitutively. In this study, the effect of elevated fructose, as a carbon source, on the MDR was evaluated. It was shown that fructose, elevated in the serum of diabetics, promotes FLC resistance. Using C. albicans strains with green fluorescent protein (GFP) tagged MDR transporters, it was determined that the FLC-resistance phenotype occurs as a result of Mdr1p activation and via the increased induction of higher Cdr1p levels. It was observed that fructose-grown C. albicans cells displayed a high efflux activity of both transporters as opposed to glucose-grown cells, which synthesize Cdr1p but not Mdr1p. Additionally, it was concluded that elevated fructose serum levels induce the de novo production of Mdr1p after 60 min. In combination with glucose, however, fructose induces Mdr1p production as soon as after 30 min. It is proposed that fructose may be one of the biochemical factors responsible for Mdr1p production in C. albicans cells.

scholarly journals Phosphorylation of MgrA and Its Effect on Expression of the NorA and NorB Efflux Pumps of Staphylococcus aureus

2010 ◽  
Vol 192 (10) ◽  
pp. 2525-2534 ◽  
Author(s):  
Que Chi Truong-Bolduc ◽  
David C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Virulence Factors ◽  
Double Mutant ◽  
Efflux Pumps ◽  
Efflux Transporters ◽  
Global Regulator ◽  
Binding Assays ◽  
Genes Encoding ◽  
Gel Shift

ABSTRACT MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrAS110A-S113A bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates.

scholarly journals Role of anacrRmutation in multidrug resistance ofin vitro-selected fluoroquinolone-resistant mutants ofSalmonella entericaserovar Typhimurium

2004 ◽  
Vol 238 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Anne Olliver ◽  
Michel Vallé ◽  
Elisabeth Chaslus-Dancla ◽  
Axel Cloeckaert
Keyword(s):  
Multidrug Resistance ◽  
Resistant Mutants
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