Perturbation of membrane microdomains in GLC4 multidrug‐resistant lung cancer cells − modification of ABCC1 (MRP1) localization and functionality

Marbeuf-Gueye, Carole; Stierlé, Vérène; Sudwan, Paiwan; Salerno, Milena; Garnier‐Suillerot, Arlette

doi:10.1111/j.1742-4658.2007.05688.x

Cited by 20 publications

(19 citation statements)

References 55 publications

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“…Recently, MRP1 was shown to be exclusively associated with light membrane fractions representing Lo phase membrane microdomains, as isolated using a detergent-free isolation procedure, in GLC4/ADR MDR small lung cancer cells (40). On the other hand, in another recent study the conclusion was reached that MRP1 is not associated to DRMs.…”

Section: B Lipid Raftsmentioning

confidence: 74%

“…Rather, these ABC transporters appear to be associated with a novel type of lipid raft, as deˆned by Lubrol WX or Brij-96 isolation. In addition, these domains may be isolated using detergent-free lipid raft isolation procedures (40). In this respect, we have recently obtained evidence for a partial localization of MRP1 in detergent-free lipid raft gradient fractions in both Neuro2a murine neuroblastoma cells and MRP-1 over expressing hamster BHK/MRP1 cells (Klappe, K., Dijkhuis, A. J., Hummel, I., Boer, A. de, Huls, A. M., Dam, A. van, Permentier, H., Kroesen, B. J., Sietsma, H., and Kok, J. W., unpublished observations).…”

Section: B Lipid Raftsmentioning

confidence: 99%

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Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

Klappe

Hummel

Kroesen

et al. 2008

TIGG

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373Trends in Glycoscience and Glycotechnology Vol. 20 No. 116 (2008) AbstractSince their discovery, lipid rafts have been implicated in several cellular functions, including protein transport in polarized cells and signal transduction. Also in multidrug resistance lipid rafts may be important with regard to the localization of ATP-binding cassette (ABC) transporters in these membrane domains. This speciˆc localization may support the activity of these ABC transporters as drug eOEux pumps and this raises important questions regarding the dependence on lipid raft constituents. In this respect, two lipid classes immediately come into play, as both sphingolipids and sterols are generally assumed to be important in the generation and maintenance of lipid rafts. Apart from lateral interactions with lipids in the membrane bilayer, one can also envision that transverse interactions with respect to the membrane bilayer play a role in positioning and function of ABC transporters. Indeed, some evidence exists for a role of the actin cytoskeleton in stabilizing the position of ABC transporters in a certain membrane area. ABC transporters may be directly linked to the actin cytoskeleton, or indirectly via lipid rafts. In this review, we will evaluate whether ABC transporters are dependent on a particular membrane environment for their function and which of the lipid raft constituents appear to be essential for this dependency.

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Section: B Lipid Raftsmentioning

confidence: 74%

Section: B Lipid Raftsmentioning

confidence: 99%

Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

Klappe

Hummel

Kroesen

et al. 2008

TIGG

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“…Apart from the effect on ATPase activity, flavonoids could possibly modulate MRP1 by inducing changes in the lipid bilayer in which this protein transporter is embedded. Previous studies have indicated that MRP1-mediated transport is not sensitive to perturbations of lipid bilayer [24][25][26][27]. To investigate the ability of the four flavonoids to change the biophysical properties of lipid bilayers, we studied their interactions with model membranes formed from phosphatidylcholine.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrated that detergents do not influence the binding and transport of a substrate by MRP1 [24,25]. In cells, MRP1 is associated with membrane microdomains enriched in glycosphingolipids, but it was shown that the changes in cholesterol [26] or glucosulceramide levels [27] did not directly modulate MRP1 function. However, cholesterol depletion below 40% caused MRP1 shift out of lipid rafts, associated with a decrease in its functionality [26].…”

Section: Introductionmentioning

confidence: 99%

“…In cells, MRP1 is associated with membrane microdomains enriched in glycosphingolipids, but it was shown that the changes in cholesterol [26] or glucosulceramide levels [27] did not directly modulate MRP1 function. However, cholesterol depletion below 40% caused MRP1 shift out of lipid rafts, associated with a decrease in its functionality [26]. Since flavonoids are known to affect lipid bilayers, and their antibacterial and antioxidant activities are believed to engage some membrane-dependent processes (see [28] for review), we decided to ask whether the perturbation of membrane biophysical properties is related to their MRP1-inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

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Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

Wesołowska

Hendrich

Łania-Pietrzak

et al. 2009

Cellular and Molecular Biology Letters

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The expression of transmembrane transporter multidrug resistance-associated protein 1 (MRP1) confers the multidrug-resistant phenotype (MDR) on cancer cells. Since the activity of the other MDR transporter, P-glycoprotein, is sensitive to membrane perturbation, we aimed to check whether the changes in lipid bilayer properties induced by flavones (apigenin, acacetin) and flavonols (morin, myricetin) were related to their MRP1 inhibitory activity. All the flavonoids inhibited the efflux of MRP1 fluorescent substrate from human erythrocytes and breast cancer cells. Morin was also found to stimulate the ATPase activity of erythrocyte ghosts. All flavonoids intercalated into phosphatidylcholine bilayers as judged by differential scanning calorimetry and fluorescence spectroscopy with the use of two carbocyanine dyes. The model of an intramembrane localization for flavones and flavonols was proposed. No clear relationship was found between the membrane-perturbing activity of flavonoids and their potency to inhibit MRP1. We concluded that mechanisms other than perturbation of the lipid phase of membranes were responsible for inhibition of MRP1 by the flavonoids.

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Lipid rafts are essential for peroxisome biogenesis in HepG2 cells†

et al. 2010

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Peroxisomes are particularly abundant in the liver and are involved in bile salt synthesis and fatty acid metabolism. Peroxisomal membrane proteins (PMPs) are required for peroxisome biogenesis [e.g., the interacting peroxisomal biogenesis factors Pex13p and Pex14p] and its metabolic function [e.g., the adenosine triphosphate-binding cassette transporters adrenoleukodystrophy protein (ALDP) and PMP70]. Impaired function of PMPs is the underlying cause of Zellweger syndrome and X-linked adrenoleukodystrophy. Here we studied for the first time the putative association of PMPs with cholesterol-enriched lipid rafts and their function in peroxisome biogenesis. Lipid rafts were isolated from Triton X-100-lysed or Lubrol WX-lysed HepG2 cells and analyzed for the presence of various PMPs by western blotting. Lovastatin and methyl-b-cyclodextrin were used to deplete cholesterol and disrupt lipid rafts in HepG2 cells, and this was followed by immunofluorescence microscopy to determine the subcellular location of catalase and PMPs. Cycloheximide was used to inhibit protein synthesis. Green fluorescent protein-tagged fragments of PMP70 and ALDP were analyzed for their lipid raft association. PMP70 and Pex14p were associated with Triton X-100-resistant rafts, ALDP was associated with Lubrol WX-resistant rafts, and Pex13p was not lipid raft-associated in HepG2 cells. The minimal peroxisomal targeting signals in ALDP and PMP70 were not sufficient for lipid raft association. Cholesterol depletion led to dissociation of PMPs from lipid rafts and impaired sorting of newly synthesized catalase and ALDP but not Pex14p and PMP70. Repletion of cholesterol to these cells efficiently reestablished the peroxisomal sorting of catalase but not ALDP. Conclusion: Human PMPs are differentially associated with lipid rafts independently of the protein homology and/or their functional interaction. Cholesterol is required for peroxisomal lipid raft assembly and peroxisome biogenesis. (HEPATOLOGY 2010;52:623-633) P eroxisomes are single membrane-bound organelles that are especially abundant in the human liver. They are involved in a wide range of metabolic processes, including b-oxidation of fatty acids, bile acid biosynthesis, plasmalogen biosynthesis, and the removal of reactive oxygen species that are Abbreviations: ABC, adenosine triphosphate-binding cassette; ALDP, adrenoleukodystrophy protein; ATP, adenosine triphosphate; DMSO, dimethyl sulfoxide; ECR, ergosterol/ceramide-rich; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; L, lovastatin; m-b-CD, methyl-b-cyclodextrin; mPTS, membrane peroxisomal targeting signal; PEX, peroxisomal biogenesis factor; PMP, peroxisomal membrane protein; TMD, transmembrane domain; VLCFA, very long chain fatty acid; X-ALD, X-linked adrenoleukodystrophy; YFP, yellow fluorescent protein; ZS, Zellweger syndrome.From the

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Perturbation of membrane microdomains in GLC4 multidrug‐resistant lung cancer cells − modification of ABCC1 (MRP1) localization and functionality

Cited by 20 publications

References 55 publications

Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

Lipid rafts are essential for peroxisome biogenesis in HepG2 cells†

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