Inhibition of multidrug/xenobiotic resistance transporter by MK571 improves dye (Fura 2) accumulation in crustacean tissues from lobster, shrimp, and isopod

Lüders, A. K.; Saborowski, Reinhard; Bickmeyer, Ulf

doi:10.1016/j.cbpc.2009.05.016

Cited by 19 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MK-571 is a pan-MRP inhibitor that effectively inhibits transport of drugs by MRP family members (Williams et al, 2002;Lüders et al, 2009;Takeuchi et al, 2012;Ferslew et al, 2014). It was found that MK-571 increased the rates of glucuronidation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide

et al. 2015

View full text Add to dashboard Cite

Active transport of glucuronide out of cells is a critical process in elimination of drugs via the glucuronidation pathway. Here, HeLa cells were stably transfected with UGT1A1 and the contributions of BCRP and MRP family transporters to the cellular efflux of chrysin glucuronide (CG) were determined. The cDNA of UGT1A1 was introduced into HeLa cells using the lentiviral transfection method. The modified cells were functional in generation of the glucuronide from chrysin. Ko143 at 10-20 mM (a dual inhibitor of BCRP and UGT1A1) caused a marked decrease (51.3%-59.7%, P < 0.01) in the excretion rate and efflux clearance of CG. Likewise, MK-571 at 5-20 mM (an inhibitor of MRPs but an activator of UGT1A1) resulted in a significant reduction in the excretion rate (18.2%-64.0%, P < 0.01) and efflux clearance (37.0%-90.2%, P < 0.001). By contrast, dipyridamole and leukotriene C4 showed no inhibitory effects on CG excretion. The chemical inhibition indicated that excretion of CG was contributed by the MRP family transporters, whereas the role of BCRP was unclear. Furthermore, short hairpin RNA-mediated silencing of a target transporter led to a marked reduction in the excretion rate of CG (38.6% for BCRP, 39.3% for MRP1, 36.4% for MRP3, and 28.7% for MRP4; P < 0.01). Transporter silencing also led to substantial decreases in the efflux clearance (44.7% for BCRP, 60.4% for MRP1, 36.7% for MRP3, and 28.7% for MRP4; P < 0.01). The gene silencing results suggested that BCRP, MRP1, MRP3, and MRP4 were significant contributors to excretion of CG.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide

et al. 2015

View full text Add to dashboard Cite

show abstract

“…MK-571 is a selective inhibitor of MRP family transporters [40,41]. Use of MK-571 (5-20 mM) led to a marked reduction in excretion rate of chrysin sulfate (38.5-64.3%, p < 0.001) (Fig.…”

Section: Effects Of Chemical Inhibitors On Sulfate Excretion In Sult2mentioning

confidence: 90%

Efflux transport of chrysin and apigenin sulfates in HEK293 cells overexpressing SULT1A3: The role of multidrug resistance-associated protein 4 (MRP4/ABCC4)

Wan

Sun

Zhang

et al. 2015

Biochemical Pharmacology

View full text Add to dashboard Cite

“…This MXR response could be due to the presence of MRP-like protein, MK being specific to this class of transporters. MK has previously been used to detect MRP-like protein transporters in many species (Gekeler et al 1995, Wu et al 2005, Bakos & Homolya 2007, Zaja et al 2008, Lüders et al 2009). A decrease of fluorescence was generally not observed, but has previously been reported in mussel haemocytes using a combination of RB and Ver (Svensson et al 2003).…”

Section: Calcein Incorporationmentioning

confidence: 99%

“…This indirect measurement method has been used for a long time and is still used for the detection of Pgplike and MRP-like activities (Neyfakh 1988, Kerboeuf et al 1999, Hamdoun et al 2004, Lüders et al 2009), as well as for the detection of MXR/MDR activity (Holland Toomey & Epel 1993, Cornwall et al 1995, Zaja et al 2006, Caminada et al 2008. The CsA and Ver are not as specific as first claimed 10 yr ago.…”

Section: Response Comparisonmentioning

confidence: 99%

“…MK is linked to the transport inhibition of the MRP family. As a recent example in invertebrates, the combination Flura 2/MK571 was used in crustacean tissues (Lüders et al 2009) to highlight MRP-like protein activity. The second MXR protein in the present study was revealed by the increase of RB fluorescence in a CsA dose-dependent response in S. droebachiensis and L. polaris.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Multixenobiotic resistance in coelomocytes from three echinoderm species

Doussantousse¹,

Pelletier²,

Beaulieu³

et al. 2011

Aquat. Biol.

View full text Add to dashboard Cite

Multixenobiotic resistance (MXR) proteins are known to be present in most living organisms, but only a few studies have been conducted on echinoderms and especially on their circulating cells, the coelomocytes. The objective of the present study was to investigate the presence of MXR activity in coelomocytes of the sea urchin Strongylocentrotus droebachiensis, the sea star Leptasterias polaris and the sea cucumber Cucumaria frondosa. Cells were exposed to fluorescent substrates (1 µM Rhodamine B [RB] The combination RB + MK induced a fluorescence increase in S. droebachiensis and C. frondosa coelomocytes. Finally, the combination CAM + MK induced a fluorescence diminution in L. polaris coelomocytes and S. droebachiensis vibratile cells. This difference in fluorescence incorporation indicated an MXR-like activity in coelomocytes, probably due to the presence of a P-glycoprotein (Pgp) and a multidrug resistance-associated protein (MRP)-like transporter. Western blot analysis was also carried out (Ab C219 and Ab C9) in order to detect potential MXR proteins using anti-MXR antibodies. Both Pgp and MRP were detected, but could not be further discriminated. MXR activity was clearly demonstrated in coelomocytes of S. droebachiensis, L. polaris and C. frondosa, although the identity of proteins responsible for this activity needs to be confirmed. KEY WORDS: Multixenobiotic resistance · MXR · Echinoderms · Coelomocytes · P-glycoprotein · Pgp · Multidrug resistance-associated proteins · MRPsResale or republication not permitted without written consent of the publisher Aquat Biol 12: 81-96, 2011 Pgp is known to be the primary active transporter of unmodified xenobiotics (Zaja et al. 2007), transporting mostly large and moderately hydrophobic cations (Litman et al. 2001). It is widely distributed in tissues and has a variety of physiological roles in healthy cells, such as lipid transport, intracellular cholesterol trafficking and the cytotoxic activity of NK and T cells (Johnstone et al. 2000). Among the family of MRPs, MRP1 facilitates the extrusion of numerous glutathione, glucuronate and sulphate conjugates. MRP1 is a ubiquitous protein taking part in various physiological functions including defence against xenobiotics and endogenous toxic metabolites, leukotrienemediated inflammatory responses, as well as protection from the toxic effect of oxidative stress (Bakos & Homolya 2007).A combination of substrates and inhibitors is often used to indicate MXR activity (Neyfakh 1988, Cornwall et al. 1995, Marin et al. 2004). Since some substrates and inhibitors are more specific to one MXR protein than to another, it is sometimes possible to discriminate the proteins involved. For example, Rhodamine B (RB) is often used as a Pgp substrate (Minier & Moore 1996, Reungpatthanaphong et al. 2003, Zaja et al. 2006) and a similar molecule, Rhodamine 123, is used as a Pgp-and MRP-like substrate (Hollo et al. 1996, Daoud et al. 2000. Calcein-AM (CAM) is also known as a substrate for both Pgp-like and MRP-like proteins,...

show abstract

Inhibition of multidrug/xenobiotic resistance transporter by MK571 improves dye (Fura 2) accumulation in crustacean tissues from lobster, shrimp, and isopod

Cited by 19 publications

References 27 publications

Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide

Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide

Efflux transport of chrysin and apigenin sulfates in HEK293 cells overexpressing SULT1A3: The role of multidrug resistance-associated protein 4 (MRP4/ABCC4)

Multixenobiotic resistance in coelomocytes from three echinoderm species

Contact Info

Product

Resources

About