scholarly journals MRP2, a human conjugate export pump, is present and transports fluo 3 into apical vacuoles of Hep G2 cells

2000 ◽  
Vol 278 (4) ◽  
pp. G522-G531 ◽  
Author(s):  
Tobias Cantz ◽  
Anne T. Nies ◽  
Manuela Brom ◽  
Alan F. Hofmann ◽  
Dietrich Keppler
Keyword(s):  
Multidrug Resistance ◽  
Bile Salt ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Membrane Expression ◽  
Reverse Transcription Pcr ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
G2 Cells ◽  
Apical Vacuole

The multidrug resistance protein 2 (MRP2, symbol ABCC2) transports anionic conjugates and certain amphiphilic anions across the apical membrane of polarized cells. Human hepatoma Hep G2 cells retain hepatic polarity and form apical vacuoles into which cholephilic substances are secreted. Immunofluorescence microscopy showed that human MRP2 was expressed in the apical vacuole membrane of polarized Hep G2 cells, whereas the isoform MRP3 was localized to the lateral membrane. Expression of both MRP2 and MRP3 was confirmed by immunoblotting and reverse transcription PCR. Fluo 3 secretion into the apical vacuoles was inhibited by cyclosporin A but not by selective inhibitors of multidrug resistance 1 P-glycoprotein. In addition, carboxyfluorescein, rhodamine 123, and the fluorescent bile salt derivatives ursodeoxycholyl-(Nε-nitrobenzoxadiazolyl)-lysine and cholylglycylamido-fluorescein were secreted into the apical vacuoles; the latter two probably via the bile salt export pump. We conclude that MRP2 mediates fluo 3 secretion into the apical vacuoles of polarized Hep G2 cells. Thus the function of human MRP2 and the action of inhibitors can be analyzed by the secretion of fluorescent anions such as fluo 3.

scholarly journals The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

2020 ◽  
Vol 21 (7) ◽  
pp. 2630
Author(s):  
Francisco V.C. Mello ◽  
Gabriela N. de Moraes ◽  
Raquel C. Maia ◽  
Jennifer Kyeremateng ◽  
Surtaj Hussain Iram ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporters ◽  
Graphene Quantum Dots ◽  
Atp Binding ◽  
Multidrug Resistance Protein ◽  
Membrane Expression ◽  
Multidrug Resistance Protein 1 ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
Atp Binding Cassette

The cancer multidrug resistance is involved in the failure of several treatments during cancer treatment. It is a phenomenon that has been receiving great attention in the last years due to the sheer amount of mechanisms discovered and involved in the process of resistance which hinders the effectiveness of many anti-cancer drugs. Among the mechanisms involved in the multidrug resistance, the participation of ATP-binding cassette (ABC) transporters is the main one. The ABC transporters are a group of plasma membrane and intracellular organelle proteins involved in the process of externalization of substrates from cells, which are expressed in cancer. They are involved in the clearance of intracellular metabolites as ions, hormones, lipids and other small molecules from the cell, affecting directly and indirectly drug absorption, distribution, metabolism and excretion. Other mechanisms responsible for resistance are the signaling pathways and the anti- and pro-apoptotic proteins involved in cell death by apoptosis. In this study we evaluated the influence of three nanosystem (Graphene Quantum Dots (GQDs), mesoporous silica (MSN) and poly-lactic nanoparticles (PLA)) in the main mechanism related to the cancer multidrug resistance such as the Multidrug Resistance Protein-1 and P-glycoprotein. We also evaluated this influence in a group of proteins involved in the apoptosis-related resistance including cIAP-1, XIAP, Bcl-2, BAK and Survivin proteins. Last, colonogenic and MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assays have also been performed. The results showed, regardless of the concentration used, GQDs, MSN and PLA were not cytotoxic to MDA-MB-231 cells and showed no impairment in the colony formation capacity. In addition, it has been observed that P-gp membrane expression was not significantly altered by any of the three nanomaterials. The results suggest that GQDs nanoparticles would be suitable for the delivery of other multidrug resistance protein 1 (MRP1) substrate drugs that bind to the transporter at the same binding pocket, while MSN can strongly inhibit doxorubicin efflux by MRP1. On the other hand, PLA showed moderate inhibition of doxorubicin efflux by MRP1 suggesting that this nanomaterial can also be useful to treat MDR (Multidrug resistance) due to MRP1 overexpression.

Glutamic Acid Uptake Inhibition Assay in Cultured Hep G2 Cells as an Alternative Method for Evaluating Potential In Vivo Eye Irritation

1989 ◽  
Vol 16 (4) ◽  
pp. 344-352
Author(s):  
Paul J. Dierickx
Keyword(s):  
Glutamic Acid ◽  
Corneal Opacity ◽  
Acid Uptake ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Eye Irritation ◽  
Uptake Inhibition ◽  
Range Finding ◽  
G2 Cells

Glutamic acid (GA) content was measured in cultured Hep G2 cells, after treatment of the cells with test compounds. The results with 37 chemicals were compared with their respective rabbit eye irritation data, of which 17 were determined according to the OECD test, and the other 20 in range-finding studies. The chemicals were mainly organic solvents (alcohols, esters, amines, acids and others). The xenobiotics were applied to the cells for 4 hours at 5 different concentrations. The cells were then incubated for 15 minutes with tritiated GA. GA uptake inhibition was measured by liquid scintillation counting, and the results were expressed as the GI50 value, which is the concentration of test compound required to induce a 50% reduction in GA uptake. A linear correlation coefficient r = 0.66 was found between the log GI50 and the mean corneal opacity scores. This value is comparable to that obtained in total protein and uridine uptake inhibition studies. However, r = 0.81 was found when the log GI50 was compared with range-finding scores, indicating that a closer relationship exists between cytotoxicity and the latter.

scholarly journals Human proapolipoprotein A-II is cleaved following secretion from Hep G2 cells by a thiol protease.

1984 ◽  
Vol 259 (24) ◽  
pp. 15556-15563 ◽  
Author(s):  
J I Gordon ◽  
H F Sims ◽  
C Edelstein ◽  
A M Scanu ◽  
A W Strauss
Keyword(s):  
Hep G2 ◽  
Hep G2 Cells ◽  
Thiol Protease ◽  
G2 Cells

The Hep G2 Cell Line as a Possible Alternative to Isolated Hepatocytes in Cytotoxicity Studies

1988 ◽  
Vol 16 (1) ◽  
pp. 16-22
Author(s):  
Marina Marinovich ◽  
Jose L. Lorenzo ◽  
Liliana M. Flaminio ◽  
Agnese Granata ◽  
Corrado L. Galli
Keyword(s):  
Cell Line ◽  
Rat Hepatocytes ◽  
Prostaglandin E ◽  
Human Hepatoma ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Isolated Rat Hepatocytes ◽  
G2 Cells ◽  
Isolated Rat

The hepatotoxicity of carbon tetrachloride (CC14) was evaluated in vitro in freshly isolated rat hepatocytes and in the human hepatoma cell line, Hep G2. Toxicity was assessed by the leakage of cytosolic enzymes (lactate dehydrogenase and aspartate aminotransferase) and cell viability (trypan blue exclusion). The established human cells were less sensitive to CCl4-induced injury; higher doses of the toxic agent and longer incubation times were necessary to elicit cell damage. Micromolar concentrations of prostaglandin E2 significantly decreased enzyme leakage in both Hep G2 cells and rat hepatocytes challenged with CC14; a stable derivative of prostacyclin (ZK 36374) was ineffective. These results suggest that human hepatoma Hep G2 cells may represent a valid alternative to isolated rat hepatocytes for an initial approach to the in vitro evaluation of cell toxicity.

scholarly journals The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly.

1990 ◽  
Vol 265 (18) ◽  
pp. 10556-10564 ◽  
Author(s):  
J Borén ◽  
M Wettesten ◽  
A Sjöberg ◽  
T Thorlin ◽  
G Bondjers ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells ◽  
Lipoprotein Assembly

scholarly journals Studies of the sites of intracellular degradation of apolipoprotein B in Hep G2 cells.

1992 ◽  
Vol 267 (31) ◽  
pp. 22630-22638 ◽  
Author(s):  
S Furukawa ◽  
N Sakata ◽  
H.N. Ginsberg ◽  
J.L. Dixon
Keyword(s):  
Apolipoprotein B ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Intracellular Degradation ◽  
G2 Cells

Ankaflavin fromMonascus-Fermented Red Rice Exhibits Selective Cytotoxic Effect and Induces Cell Death on Hep G2 Cells

2005 ◽  
Vol 53 (6) ◽  
pp. 1949-1954 ◽  
Author(s):  
Nan-Wei Su ◽  
Yii-Lih Lin ◽  
Min-Hsiung Lee ◽  
Chen-Ying Ho
Keyword(s):  
Cell Death ◽  
Cytotoxic Effect ◽  
Red Rice ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells
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