1,720,967 research outputs found
Alteration of intracellular cholesterol in skin fibroblasts from Alzheimer’s Disease patients
Neutral lipids accumulation in peripheral blood mononuclear cells: hallmark of Alzheimer’s Disease?
Inhibition of cholesterol esterification influences cholesterol metabolism and infiammatory response in lipopolysacharide-activated P388D1 macrophages
INHIBITION OF CHOLESTEROL ESTERIFICATION INCREASES CHOLESTERYL ESTER UPTAKE FROM HDL IN PARENTAL AND MDR1 RESISTANT CCRF-CEM CELLS
Objectives: Cholesteryl ester (CE) content is elevated in cancer cells, while
tumour bearing subjects show low levels of HDL. We have previously
demonstrated that cancer cells also acquire CEs from HDL (1, 2). In the
present study we further investigated this aspect in a lymphoblastic CCRFCEM
cell line
Methods: As multidrug-resistant P-glycoprotein-MDR1 has been involved
in CE metabolism (3), CEM were made resistant by stepwise exposure to
low (LR, 50nM) and high (HR, 500nM) doses of vincristine. We evaluated:
P-gp activity (3H-vinblastine), CE content (HPLC), CE synthesis (14C-oleate),
neutral lipid and Dil-HDL uptake (fluorescence), ACAT and SR-B1 protein
expression (western blotting). The ACAT inhibitor Sandoz-58035 (SZ,
4mM), progesterone (PG, 20mM), the P-gp inhibitors cyclosporine (CLS,
2,5mM) and verapamil (VPM, 10mM), were used as inhibitors of CE
synthesis.
Results: CE content in LR was similar to parental, whereas it was significantly
higher in HR cells. However, CE synthesis and the ACAT protein
expression were similar in all groups. SZ completely inhibited CE synthesis
but not proliferation and P-gp activity. PG blocked CE synthesis and proliferation
but failed to revert MDR-resistance. CLS and VPM reversed MDRresistance,
inhibited CE synthesis and proliferation in LR, but were highly
toxic in HR cells. A higher content of neutral lipids was found in presence of
all inhibitors. Except for SZ, the drugs leaded to a higher CE content, CEHDL
uptake and SR-B1 protein expression then the respective controls.
These effects were more evident in MDR cells.
Conclusion: Our data suggest that HDL, rather than removing, may supply
via SR-B1 the increase requirements of CEs in cancer cells. CE uptake is
even increased when CE endogenous synthesis is inhibited, making HDL a
promising tool for delivering antitumor drugs
Possible role of P-glycoprotein MDR1 in controlling cancer cell esterification by modulating cholesteryl ester uptake from HDL
A source of cholesteryl esters (CEs) is essential for an efficient antimicrobial response in lypopolisacharide-activated P388D1 macrophages
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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