Search results for "Member 1"
showing 10 items of 102 documents
Association of selected ABC gene family single nucleotide polymorphisms with postprandial lipoproteins: results from the population-based Hortega stu…
2009
The aim of the study was to determine the influence of twenty single nucleotide polymorphisms (SNPs) of the ABCA1, ABCG1, ABCG5 and ABCG8 genes on the plasmatic concentrations of total cholesterol (TC), HDL and LDL cholesterol (HDLc, LDLc) in the postprandial state with a representative Spanish Caucasian population (1473 individuals, 50.0% women, ages ranging 21-85 years). In men, subjects with the AA genotype of the ABCA1 rs2230806 (R219K) polymorphism were associated with increased plasma LDLc levels, while the ABCA1 haplotype, which included the rs2230806 A allele, was associated with higher TC and LDLc plasma concentrations. In women, significant relationships were found between rs18935…
Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
2014
The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice deleted for transcription intermediary factor 1γ (Tif1γ) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1γ is down-regulated in HSCs during aging in 20-mo-old wild-type mice. We established that Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1γ(-/-) and old HSCs are more sensitive to TGF-β signaling. Importantly, we identified two populations of HSCs specifical…
Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial B…
2014
International audience; The objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitoch…
Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice
2010
Abstract Background P-glycoprotein (P-gp), an efflux transporter localized in the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). For the new antipsychotic aripiprazole and its active metabolite dehydroaripiprazole differences in disposition in blood and brain were investigated after acute and sub-chronic administration in a P-gp knockout mouse model. Methods Serum and brain concentrations of both drugs were measured at several time points 1–24 h after i.p. injection of 10 mg/kg aripiprazole and after 11 days of sub-chronic administration in several tissues. Moreover, the expression of P-gp was determined by Western blot analysis after sub…
Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking
2015
Apigenin is a common dietary flavonoid with considerable cytotoxic activity in vitro and in vivo. Despite many mechanistic studies, less is known about resistance factors hampering apigenin's activity. We investigated the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5. Multidrug-resistant cells overexpressing these ABC transporters were not cross-resistant toward apigenin. Moreover, apigenin inhibited not only P-glycoprotein but also BCRP by increasing cellular uptake of doxorubicin and synergistic inhibition of cell viability in combination with doxorubicin or docetaxel in multidrug-resistant cells. To perform in silico molecular docki…
Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It
2021
Drug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guida…
Antioxidant defenses in a B16 melanoma line resistant to doxorubicin: an in vivo study.
1991
A B16 melanoma line was repeatedly transplanted subcutaneously in C57BL/6 mice. On day 4 after every transplant, the animals were treated with doxorubicin (DXR), 10 mg/kg i.p. The aim of the work was to develop an in-vivo model of resistance to the antiblastic in order to analyze some possible mechanistic aspects of the process in the course of time. After 16 transplants and treatments the melanoma completely lost its sensitivity to the antiproliferative effects of maximal tolerated doses of DXR and showed over-expression of P-glycoprotein. Compared to the parental line, the in vitro resistance index was 4.6. After 27 transplants and treatments the melanoma did not increase its in vitro res…
Selective induction of apoptosis in multidrug resistant HL60R cells by the thiazolobenzoimidazole derivative 1-(2,6-difluorophenyl)-1H,3H-thiazolo [3…
1999
We investigated the antitumour effects of 1-(2,6-difluorophenyl)-1H,3H-thiazolo [3,4-a]benzimidazole (TBZ) a new anti-HIV-1 agent, on human promyelocytic HL60 leukaemia, both a parental and a multidrug resistant form (HL60R). HL60R overexpresses P-glycoprotein and, like HL60, lacks p53 protein expression. HL60 and HL60R show similar levels of Bcl-2 protein. In contrast to the conventional chemotherapeutic agents daunorubicin, etoposide and mitoxantrone, TBZ caused equal or even greater cytotoxicity in HL60R than in HL60, and this result was associated with a more marked induction of apoptosis in the drug resistant cells. The antitumour activity of TBZ occurred in the range of concentrations…
Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and…
2002
We studied the human HL60 leukemia cell line and its multidrug resistant (MDR) variant HL60R. In contrast to the HL60, HL60R showed an inability to undergo apoptosis from doxorubicin (Dox) or other different stimuli, including cisplatin, Fas ligation and serum withdrawal. HL60R cells lost surface Fas expression, but we found no evidence that Fas/FasL mediates the apoptotic effects of Dox in HL60. P-glycoprotein (P-gp) did not seem to play a major role as a specific inhibitor of apoptosis. In fact, the P-gp inhibitor verapamil reversed only partially the resistance to Dox-induced apoptosis of the MDR cells. In addition, it did not modify the rate of apoptosis induced from the other stimuli i…
Role of the tumor microenvironment in the activity and expression of the p-glycoprotein in human colon carcinoma cells.
2006
The metabolic microenvironment of solid tumors is characterized by an oxygen deficiency and increased anaerobic glycolysis leading to extracellular acidosis and ATP depletion, which in turn may affect other energy-dependent cellular pathways. Since many tumors overexpress active drug transporters (e.g. the p-glycoprotein) leading to a multidrug-resistant phenotype, this study analyzes the impact of the different aspects of the extracellular microenvironment (hypoxia and acidosis) on the activity and expression of the p-glycoprotein (pGP) in the human colon carcinoma cell line LS513. For up to 24 h cells were exposed to hypoxia (pO2<0.5 mmHg), an acidic extracellular environment (pH 6.6), or…