Divergent Effects of Nitric Oxide Donors on the Biliary Efflux Transporters in Isolated Perfused Rat Livers: Nitric Oxide-Independent Inhibition of ABC Transporters by Sodium Nitroprusside

Parasrampuria, Ridhi; Mehvar, Reza

doi:10.2174/187231211794455244

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…In addition, the specific NO scavenger PTIO did not reverse the SNPinduced alteration of P-gp function, indicating that the effect of SNP on P-gp function occurred via an NO-independent mechanism [29] . This result agreed with previous studies performed in isolated perfused rat livers [32] . Furthermore, a significant increase in intracellular ROS (iROS) and RNS (iRNS) in Caco-2 cells was observed at early stages of SNP exposure, which indicated that iROS and iRNS were involved in the SNP-induced impairment of P-gp function.…”

Section: Discussionsupporting

confidence: 94%

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells

Duan

Liu

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the effects of nitric oxide (NO) donors on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. Methods: Caco-2 cells were exposed to NO donors for designated times. P-gp function and expression were assessed using Rhodamine123 uptake assay and Western blotting, respectively. Intracellular reactive oxygen species (iROS) and intracellular reactive nitrogen species (iRNS) levels were measured using ROS and RNS assay kits, respectively. Results: Exposure of Caco-2 cells to 0.1 or 2 mmol/L of sodium nitroprusside (SNP) affected the function and expression of P-gp in concentration-and time-dependent manners. A short-term (4 h) exposure reduced P-gp function and expression accompanied with significantly increased levels of iROS and iRNS. In contrast, a long-term (24 h) exposure stimulated the P-gp function and expression. The stimulatory effects of 2 mmol/L SNP was less profound as compared to those caused by 0.1 mmol/L SNP. The other NO donors SIN-1 and SNAP showed similar effects. Neither the NO scavenger PTIO (2 mmol/L) nor soluble guanylate cyclase inhibitor ODQ (50 µmol/L) reversed the SNP-induced alteration of P-gp function. On the other hand, free radical scavengers ascorbate, glutathione and uric acid (2 mmol/L for each), PKC inhibitor chelerythrine (5 µmol/L), PI3K/Akt inhibitor wortmannin (1 µmol/L) and p38 MAPK inhibitor SB203580 (10 µmol/L) reversed the upregulation of P-gp function by the long-term exposure to SNP, but these agents had no effect on the impaired P-gp function following the short-term exposure to SNP. Conclusion: NO donors time-dependently regulate P-gp function and expression in Caco-2 cells: short-term exposure impairs P-gp function and expression, whereas long-term exposure stimulates P-gp function and expression. The regulation occurs via a NO-independent mechanism.

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Section: Discussionsupporting

confidence: 94%

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells

Duan

Liu

et al. 2012

Acta Pharmacol Sin

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“…1 The mechanisms associated with multidrug resistance in cancer have been widely explored, and chemotherapy-induced upregulation of P-glycoprotein is considered the major event in establishing multidrug resistance in cancer cells. 2 Much research attention has been focused on the discovery and development of agents that can inhibit P-glycoprotein with high efficiency and low toxicity.…”

Section: Introductionmentioning

confidence: 99%

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Chen¹

2012

IJN

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Background: Multidrug resistance is the main obstacle to the efficiency of systemic chemotherapy against hematologic malignancy. This study investigated the reversible effect of the copolymer wogonin and daunorubicin coloaded into Fe 3 O 4 magnetic nanoparticles, and the mechanism potentially involved. Methods: The growth inhibition rate of K562/A02 cells was investigated by MTT assay, and apoptosis of cells and the intracellular daunorubicin concentration were detected by flow cytometry. Distribution of nanoparticles taken up by K562/A02 cells was observed under a transmission electron microscope and demonstrated by Prussian blue staining. The transcription level of MDR1 mRNA and expression of P-glycoprotein were determined by reverse transcriptase polymerase chain reaction and Western blotting assay, respectively. Results: The reversible effect of daunorubicin-wogonin magnetic nanoparticles was 8.87-fold that of daunorubicin + wogonin and of daunorubicin magnetic nanoparticles. Transmission electron microscopy and Prussian blue staining revealed that the nanoparticles were located in the endosome vesicles of cytoplasm. Also, the apoptosis rate and accumulation of intracellular daunorubicin in the daunorubicin-wogonin magnetic nanoparticle group were significantly higher than that in the daunorubicin, daunorubicin + wogonin, and daunorubicin magnetic nanoparticle groups. Furthermore, transcription of MDR1 mRNA and expression of P-glycoprotein in K562/ A02 cells were significantly downregulated in the daunorubicin-wogonin magnetic nanoparticle group compared with the other groups. Conclusion: These findings suggest that the remarkable effects of the novel daunorubicinwogonin magnetic nanoparticle formulation on multidrug resistant K562/A02 leukemia cells would be a promising strategy for overcoming multidrug resistance.

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RETRACTED: Effect of ST3GAL 4 and FUT 7 on sialyl Lewis X synthesis and multidrug resistance in human acute myeloid leukemia

Zhou

Song

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Sialyl Lewis X (sLe X, CD15s) is a key antigen produced on tumor cell surfaces during multidrug resistance (MDR) development. The present study investigated the effect of α1, 3 fucosyltransferase VII (FucT VII) and α2, 3 sialyltransferase IV (ST3Gal IV) on sLe X oligosaccharides synthesis as well as their impact on MDR development in acute myeloid leukemia cells (AML). FUT7 and ST3GAL4 were overexpressed in three AML MDR cells and bone marrow mononuclear cells (BMMC) of AML patients with MDR by real-time polymerase chain reaction (PCR). A close association was found between the expression levels of FUT7 and ST3GAL4 and the amount of sLe X oligosaccharides, as well as the phenotypic variation of MDR of HL60 and HL60/ADR cells both in vitro and in vivo. Manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, thereby regulating the proportionally mutative expression of P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1), both of which are known to be involved in MDR. Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or Akt short hairpin RNA (shRNA) resulted in the reduced MDR of HL60/ADR cells. This study indicated that sLe X involved in the development of MDR of AML cells probably through FUT7 and ST3GAL4 regulating the activity of PI3K/Akt signaling pathway and the expression of P-gp and MRP1.

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Divergent Effects of Nitric Oxide Donors on the Biliary Efflux Transporters in Isolated Perfused Rat Livers: Nitric Oxide-Independent Inhibition of ABC Transporters by Sodium Nitroprusside

Cited by 5 publications

References 35 publications

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

RETRACTED: Effect of ST3GAL 4 and FUT 7 on sialyl Lewis X synthesis and multidrug resistance in human acute myeloid leukemia

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