'Multidrug transporters play a dual role in haematopoietic cells, mediating the efflux of xenobiotics and regulating cell migration. For several reasons including the lack of specific antibodies, reports of multidrug transporter distribution on lymphocytes conflict. Murine B cells have been reported to completely lack transporter activity. Through analysis of parental ... More
Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes.
AuthorsElliott JI, Surprenant A, Marelli-Berg FM, Cooper JC, Cassady-Cain RL, Wooding C, Linton K, Alexander DR, Higgins CF
JournalNat Cell Biol
PubMed ID16025105
'Phosphatidylserine (PS) exposure is normally associated with apoptosis and the removal of dying cells. We observed that PS is exposed constitutively at high levels on T lymphocytes that express low levels of the transmembrane tyrosine phosphatase CD45RB. CD45 was shown to be a negative regulator of PS translocation in response ... More
A silent polymorphism in the MDR1 gene changes substrate specificity.
AuthorsKimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM,
JournalScience
PubMed ID17185560
'Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of ... More
D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains.
AuthorsMakino A, Ishii K, Murate M, Hayakawa T, Suzuki Y, Suzuki M, Ito K, Fujisawa T, Matsuo H, Ishitsuka R, Kobayashi T
JournalBiochemistry
PubMed ID16584188
'D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is a frequently used inhibitor of glycosphingolipid biosynthesis. However, some interesting characteristics of D-PDMP cannot be explained by the inhibition of glycolipid synthesis alone. In the present study, we showed that d-PDMP inhibits the activation of lysosomal acid lipase by late endosome/lysosome specific lipid, bis(monoacylglycero)phosphate (also called as ... More
Use of fluorochrome-tagged taxol to produce fluorescent microtubules in solution.
AuthorsMelan MA
JournalBiotechniques
PubMed ID9714874
Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo.
AuthorsFellner S, Bauer B, Miller DS, Schaffrik M, Fankhänel M, Spruss T, Bernhardt G, Graeff C, Färber L, Gschaidmeier H, Buschauer A, Fricker G
JournalJ Clin Invest
PubMed ID12417570
Paclitaxel concentrations in the brain are very low after intravenous injection. Since paclitaxel is excluded from some tumors by p-glycoprotein (p-gp), the same mechanism may prevent entry into the brain. In vitro, paclitaxel transport was examined in capillaries from rat brains by confocal microscopy using BODIPY Fl-paclitaxel. Western blots and ... More
Chemical synthesis and biological activity of a novel fluorescent etoposide derivative.
AuthorsLazo JS, Li T, Woo ES, Settineri CE, Allan WP, Yalowich JC
JournalBiochem Pharmacol
PubMed ID9113091
The antineoplastic activity of etoposide resides in its ability to poison the nuclear enzyme DNA topoisomerase II (topo II). The factors that control the cellular entry and subcellular distribution of etoposide remain poorly understood. Therefore, we have synthesized a novel fluorescence-labeled etoposide (Bodipyetoposide) by coupling 4,4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-propionylethylenediamine (Bodipy) to 4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin ... More
The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models.
AuthorsMartin C, Walker J, Rothnie A, Callaghan R
JournalBr J Cancer
PubMed ID14562035
Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? ... More
Calcium-mediated transductive systems and functionally active gap junctions in astrocyte-like GL15 cells.
AuthorsMariggio MA, Mazzoleni G, Pietrangelo T, Guarnieri S, Morabito C, Steimberg N, Fano G
JournalBMC Physiol
PubMed ID11384510
BACKGROUND: It has been proposed that GL15, a human cell line derived from glioblastoma multiforme, is a possible astroglial-like cell model, based on the presence of cytoplasmic glial fibrillary acidic protein. RESULTS: The aim of this work was to delineate the functional characteristics of GL15 cells using various experimental approaches, ... More