scholarly journals Aspirin influences megakaryocytic gene expression leading to up‐regulation of multidrug resistance protein‐4 in human platelets

2014 ◽  
Vol 78 (6) ◽  
pp. 1343-1353 ◽  
Author(s):  
Isabella Massimi ◽  
Raffaella Guerriero ◽  
Lavinia Vittoria Lotti ◽  
Valentina Lulli ◽  
Alessandra Borgognone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Human Platelets ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

Multidrug resistance protein gene expression inTrichoplusia nicaterpillars

2012 ◽  
Vol 22 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Jason Simmons ◽  
Olivia D'Souza ◽  
Mark Rheault ◽  
Cam Donly
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Protein Gene ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

scholarly journals Aspirin Extrusion From Human Platelets Through Multidrug Resistance Protein-4–Mediated Transport

2011 ◽  
Vol 58 (7) ◽  
pp. 752-761 ◽  
Author(s):  
Teresa Mattiello ◽  
Raffaella Guerriero ◽  
Lavinia Vittoria Lotti ◽  
Elisabetta Trifirò ◽  
Maria Pia Felli ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Human Platelets ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets

2016 ◽  
Vol 76 ◽  
pp. 11-17 ◽  
Author(s):  
Flavia Temperilli ◽  
Manuela Di Franco ◽  
Isabella Massimi ◽  
Maria Luisa Guarino ◽  
Maria Paola Guzzo ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Human Platelets ◽  
Multidrug Resistance Protein ◽  
Inflammatory Drugs ◽  
Resistance Protein ◽  
In Vivo Treatment ◽  
Anti Inflammatory

Increased efflux of glutathione conjugate in acutely diabetic cardiomyocytes

2004 ◽  
Vol 82 (10) ◽  
pp. 879-887 ◽  
Author(s):  
Sanjoy Ghosh ◽  
Simon Ting ◽  
Howard Lau ◽  
Thomas Pulinilkunnil ◽  
Ding An ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Multidrug Resistance Protein ◽  
Multidrug Resistance Protein 1 ◽  
Resistance Protein

In diabetes, cell death and resultant cardiomyopathy have been linked to oxidative stress and depletion of antioxidants like glutathione (GSH). Although the de novo synthesis and recycling of GSH have been extensively studied in the chronically diabetic heart, their contribution in modulating cardiac oxidative stress in acute diabetes has been largely ignored. Additionally, the possible contribution of cellular efflux in regulating GSH levels during diabetes is unknown. We used streptozotocin to make Wistar rats acutely diabetic and after 4 days examined the different processes that regulate cardiac GSH. Reduction in myocyte GSH in diabetic rats was accompanied by increased oxidative stress, excessive reactive oxygen species, and an elevated apoptotic cell death. The effect on GSH was not associated with any change in either synthesis or recycling, as both γ-glutamylcysteine synthetase gene expression (responsible for bio syn thesis) and glutathione reductase activity (involved with GSH recycling) remained unchanged. However, gene expression of multidrug resistance protein 1, a transporter implicated in effluxing GSH during oxidative stress, was elevated. GSH conjugate efflux mediated by multidrug resistance protein 1 also increased in diabetic cardiomyocytes, an effect that was blocked using MK-571, a specific inhibitor of this transporter. As MK-571 also decreased oxidative stress in diabetic cardiomyocytes, an important role can be proposed for this transporter in GSH and reactive oxygen species homeostasis in the acutely diabetic heart. Key words: cardiomyocytes, apoptosis, multidrug resistance protein, reactive oxygen species.

scholarly journals Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retina

2021 ◽  
Author(s):  
Kyung Woo Kim ◽  
Sentaro Kusuhara ◽  
Atsuko Katsuyama-Yoshikawa ◽  
Sho Nobuyoshi ◽  
Megumi Kitamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Retinal Cell ◽  
Mouse Retina ◽  
Retinal Layer ◽  
Multidrug Resistance Protein ◽  
Resistance Protein ◽  
Pathway Analyses ◽  
Effects Of Aging ◽  
Differently Expressed Genes

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the 4 age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

scholarly journals Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 455
Author(s):  
Kyung Woo Kim ◽  
Sentaro Kusuhara ◽  
Atsuko Katsuyama-Yoshikawa ◽  
Sho Nobuyoshi ◽  
Megumi Kitamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Retinal Cell ◽  
Retinal Layer ◽  
Multidrug Resistance Protein ◽  
Infection Pathways ◽  
Resistance Protein ◽  
Pathway Analyses ◽  
Energy Dependent ◽  
Differently Expressed Genes

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8–12 weeks (young) or 45–55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

scholarly journals Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Isabella Massimi ◽  
Ambra Ciuffetta ◽  
Flavia Temperilli ◽  
Francesca Ferrandino ◽  
Alessandra Zicari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Multidrug Resistance Protein ◽  
Cell Toxicity ◽  
Hek 293 ◽  
Dose Aspirin ◽  
Resistance Protein ◽  
High Dose Aspirin

Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α(PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.

Release of Platelet-Derived Sphingosine-1-Phosphate Involves Multidrug Resistance Protein 4 (MRP4/ABCC4) and Is Inhibited by Statins

2018 ◽  
Vol 118 (01) ◽  
pp. 132-142 ◽  
Author(s):  
Katja Vogt ◽  
Shailaja Mahajan-Thakur ◽  
Robert Wolf ◽  
Susanne Bröderdorf ◽  
Conny Vogel ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Ex Vivo ◽  
Membrane Vesicles ◽  
Human Platelets ◽  
Guanosine Monophosphate ◽  
Lipid Mediator ◽  
Multidrug Resistance Protein ◽  
Sphingosine 1 Phosphate ◽  
Resistance Protein

AbstractSphingosine-1-phosphate (S1P) is a potent lipid mediator released from activated platelets by an adenosine triphosphate (ATP)-dependent export mechanism. A candidate transport protein is the multidrug resistance protein 4 (MRP4/ABCC4), an ATP-dependent transporter highly expressed in platelets. Furthermore, several statins are known to affect platelet functions and exhibit antithrombotic properties. This study determines the involvement of MRP4 in the transport of S1P and a possible interference by statins. Transport studies in membrane vesicles of Sf9 cells containing recombinant human MRP4 revealed that MRP4 mediates ATP-dependent transport of fluorescein- and tritium-labelled S1P. Also, ATP-dependent S1P transport in platelet membrane vesicles containing endogenous MRP4 was inhibited by the MRP inhibitor MK571 and the MRP4-selective compound Ceefourin-1. Confocal microscopy using fluorescein-labelled S1P as well as boron-dipyrromethene (BODIPY)-labelled sphingosine indicated association of S1P and MRP4 in human platelets. In MRP4-deficient mice, agonist-induced S1P secretion was reduced compared with matched wild-type C57Bl/6 mice and platelet S1P concentrations were lower. Fluvastatin and rosuvastatin interfered with MRP4 function inhibiting ATP-dependent cGMP (cyclic guanosine monophosphate) uptake into MRP4-containing vesicles, inhibited MRP4-mediated S1P transport in vitro and significantly attenuated endogenous S1P release from agonist-activated platelet ex vivo. These data suggest that release of S1P from platelets depends on MRP4 and statins can interfere with this transport process. Potentially, this may be relevant for the pleiotropic anti-inflammatory effects of statins and their effect on modulating atherothrombosis.

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