A5102861822- Drug Transport and Resistance Mechanisms
- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Peptidase Inhibition and Analysis
- Caveolin-1 and cellular processes
- Cholesterol and Lipid Metabolism
- Bacterial Genetics and Biotechnology
- Neonatal Health and Biochemistry
- Neuroblastoma Research and Treatments
- Glycosylation and Glycoproteins Research
- Trace Elements in Health
- Phagocytosis and Immune Regulation
- Biomedical Research and Pathophysiology
- Peroxisome Proliferator-Activated Receptors
- Cell death mechanisms and regulation
- Pharmacological Effects of Natural Compounds
- Carbohydrate Chemistry and Synthesis
- Cancer, Lipids, and Metabolism
- Circadian rhythm and melatonin
- Nitric Oxide and Endothelin Effects
- Pediatric Hepatobiliary Diseases and Treatments
- Aldose Reductase and Taurine
- Antibiotic Resistance in Bacteria
- RNA Interference and Gene Delivery
University Medical Center Groningen
2005-2014
University of Groningen
1991-2014
Center for Digestive and Liver Diseases
1991-2012
Institute of Cell Biology
2006-2011
The Netherlands Cancer Institute
1996
Resistance of Lactococcus lactis to cytotoxic compounds shares features with the multidrug resistance phenotype mammalian tumor cells. Here, we report gene cloning and functional characterization in Escherichia coli LmrA, a lactococcal structural homolog human P-glycoprotein MDR1. LmrA is 590-aa polypeptide that has putative topology six alpha-helical transmembrane segments N-terminal hydrophobic domain, followed by hydrophilic domain containing ATP-binding site. similar each two halves MDR1...
Hibernation is an energy-conserving behavior consisting of periods inhibited metabolism (‘torpor’) with lowered body temperature. Torpor bouts are interspersed by arousal periods, in which increases and temperature returns to euthermia. In deep torpor, the typically decreases 2–10 °C, major physiological immunological changes occur. One these alterations constitutes almost complete depletion circulating lymphocytes that reversed rapidly upon arousal. Here we show torpor induces storage...
E-selectin-directed targeted drug delivery was analyzed in anti-glomerular basement membrane glomerulonephritis. Liposomes conjugated with anti-E-selectin antibodies (Ab Esel liposomes) were internalized by activated endothelial cells vitro through E-selectin-mediated endocytosis. At the onset of glomerulonephritis mice, E-selectin expressed on glomerular cells, which resulted homing Ab liposomes to glomeruli after intravenous administration. Accumulation kidney 3.6 times higher than...
Abstract Ab binding to CD20 has been shown induce apoptosis in B cells. In this study, we demonstrate that rituximab sensitizes lymphoma cells Fas-induced a caspase-8-dependent manner. To elucidate the mechanism by which Rituximab affects Fas-mediated cell death, investigated rituximab-induced signaling and pathways. Rituximab-induced involved death receptor pathway proceeded Ectopic overexpression of FLIP (the physiological inhibitor pathway) or application zIETD-fmk (specific caspase-8,...
We have obtained a novel multidrug resistant cell line, derived from HT29 G(+) human colon carcinoma cells, by selection with gradually increasing concentrations of the anti-mitotic, microtubule-disrupting agent colchicine. This HT29(col) line displayed 25-fold increase in colchicine resistance and exhibited cross-resistance to doxorubicin, VP16, vincristine taxol. Immunoblotting, combined RT-PCR showed that phenotype was conferred specific overexpression protein 1. Confocal scanning laser...
Abstract Previously we have described a novel multidrug‐resistant cell line, HT29 col , which displayed over expression of the multidrug‐resistance protein 1 (MRP1) and an altered sphingolipid composition, including enhanced levels glucosylceramide (GlcCer; Kok JW, Veldman RJ, Klappe K, Koning H, Filipeanu C, Muller M. Int J Cancer 2000;87:172–8). In our study, long‐term screening revealed that, during colchicine‐induced acquisition multidrug resistance in new increases GlcCer occurred...
Abstract The sphingolipid ceramide has been recognized as an important mediator in the apoptotic machinery, and its efficient conversion to glucosylceramide associated with multidrug resistance. Therefore, inhibitors of synthase are explored tools for treatment cancer. In this study, we used d,l-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol sensitize Neuro-2a murine neuroblastoma cells microtubule-stabilizing agent paclitaxel. This resulted a synergistic inhibition viable cell...
MRP1 (ABCC1) is known to be localized in lipid rafts. Here we show two different cell lines that localization of Mrp1/MRP1 (Abcc1/ABCC1) rafts and its function as an efflux pump are dependent on cortical actin. Latrunculin B disrupts both actin stress fibers. This results partial loss from detergent-free raft fractions, internalization (Abcc1/ABCC1), reduction (Abcc1/ABCC1)-mediated efflux. Pretreatment with nocodazole prevents latrunculin B-induced all effects Mrp1 (Abcc1) activity....
We have recently shown that two ATP binding cassette (ABC) transporters are enriched in Lubrol-resistant noncaveolar membrane domains multidrug-resistant human cancer cells [Hinrichs, J. W. J., K. Klappe, I. Hummel, and Kok. 2004. ATP-binding non-caveolar detergent-insoluble glycosphingolipid-enriched (DIGs) cells. Biol. Chem. 279: 5734–5738]. Here, we show aminophospholipids relatively compared with Triton X-100-resistant domains, whereas sphingolipids the latter. Moreover, contain more...
Previous studies have indicated a role for glucosylceramide synthase (GCS) in multidrug resistance (MDR), either related to turnover of ceramide (Cer) or generation gangliosides, which modulate apoptosis and/or the activity ABC transporters. This study challenges hypothesis that gangliosides transporters and was performed two human neuroblastoma cell lines, expressing functional P-glycoprotein (Pgp) resistance-related protein 1 (MRP1). Two inhibitors GCS,...
HepG2 cells, stably transfected with MDR1 cDNA, encoding the P-glycoprotein multidrug resistance efflux pump, display an altered sphingolipid composition compared to control empty vector. The overexpressing cells a approximately 3-fold increased level of lactosylceramide and ganglioside mass. Both mRNA activity synthase were in HepG2/MDR1 cells. In conclusion, glycolipid content MDR1-transfected is caused by transcriptional up-regulation enzyme synthase.
ATP-binding cassette (ABC) transporters are known to be important factors in multidrug resistance of tumor cells. Lipid rafts have been implicated their localization the plasma membrane, where they function as drug efflux pumps. This specific may support activity ABC/Abc transporters. raises questions regarding nature and composition lipid that harbor dependence transporters—concerning activity—on raft constituents. Here we review our work past 10 years aimed at evaluating whether dependent...
Regulation of capacitative Ca 2+ entry was studied in two different multidrug resistance (MDR) protein (MRP1) overexpressing cell lines, HT29 col and GLC4/ADR. MRP1 overexpression accompanied by a decreased response to thapsigargin. Moreover, inhibition D,L ‐ threo ‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol (PDMP) abolished cells. Both PDMP the inhibitor MK571 greatly reduced InsP 3 ‐mediated 45 release from intracellular stores Again, these effects were virtually Our results point...