The Experts below are selected from a list of 15843 Experts worldwide ranked by ideXlab platform
Yongzong Yang - One of the best experts on this subject based on the ideXlab platform.
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effects of oleate on atp binding Cassette Transporter a1 expression and cholesterol efflux in thp 1 macrophage derived foam cells
Acta Biochimica et Biophysica Sinica, 2003Co-Authors: C K Tang, Junhao Yang, Guanghui Yi, Zhugang Wang, Zhonghua Yuan, Changgeng Ruan, Yongzong YangAbstract:Abstract To study the effect of oleate on ATP binding Cassette Transporter A1 (ABCA1) expression and cholesterol efflux in THP-1 macrophage-derived foam cells, after exposure of the cultured THP-1 macrophage-derived foam cells to oleate for different time, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and its protein level were determined by RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity of THP-1 macrophage-derived foam cells was detected by flow cytometry. The results showed that oleate markedly inhibited ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by a reduction in the membrane content of ABCA1. Oleate did not alter ABCA1 mRNA abundance, indicating that decreased ABCA1 transcription, enhanced mRNA decay, or impaired translation efficiency did not account for these inhibitory effects. Oleate, however, increased ABCA1 turnover when protein synthesis was blocked by cycloheximide. Oleate reduces cholesterol efflux and the level of ABCA1 protein in THP-1 macrophage-derived foam cells.
Soonkyu Chung - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivo
Circulation, 2011Co-Authors: Abraham K. Gebre, Soonkyu Chung, Janet K Sawyer, Nobuyo Maeda, John S ParksAbstract:Background—Adipose tissue (AT) is the body's largest free cholesterol reservoir and abundantly expresses ATP binding Cassette Transporter A1 (ABCA1), a key cholesterol Transporter for high-density lipoprotein (HDL) biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown. Methods and Results—Adipocyte-specific ABCA1 knockout mice (ABCA1−A/−A) were generated by crossing ABCA1floxed mice with aP2Cre transgenic mice. AT from ABCA1−A/−A mice had <10% of wild-type ABCA1 protein expression but normal hepatic and intestinal expression. Deletion of adipocyte ABCA1 resulted in a significant decrease in plasma HDL cholesterol (≈15%) and apolipoprotein A-I (≈13%) concentrations. AT from ABCA1−A/−A mice had a 2-fold increase in free cholesterol content compared with wild-type mice and failed to efflux cholesterol to apolipoprotein A-I. However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice. Incubation of wild-type AT explants with ...
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adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivoclinical perspective
Circulation, 2011Co-Authors: Soonkyu Chung, Abraham K. Gebre, Janet K Sawyer, Nobuyo Maeda, John S ParksAbstract:Background— Adipose tissue (AT) is the body's largest free cholesterol reservoir and abundantly expresses ATP binding Cassette Transporter A1 (ABCA1), a key cholesterol Transporter for high-density lipoprotein (HDL) biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown. Methods and Results— Adipocyte-specific ABCA1 knockout mice (ABCA1−A/−A) were generated by crossing ABCA1floxed mice with aP2Cre transgenic mice. AT from ABCA1−A/−A mice had <10% of wild-type ABCA1 protein expression but normal hepatic and intestinal expression. Deletion of adipocyte ABCA1 resulted in a significant decrease in plasma HDL cholesterol (≈15%) and apolipoprotein A-I (≈13%) concentrations. AT from ABCA1−A/−A mice had a 2-fold increase in free cholesterol content compared with wild-type mice and failed to efflux cholesterol to apolipoprotein A-I. However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice. Incubation of wild-type AT explants with apolipoprotein A-I resulted in the formation of multiple discrete-sized nascent HDL particles ranging in diameter from 7.1 to 12 nm; similar incubations with ABCA1−A/−A AT explants resulted in nascent HDL <8 nm. Plasma decay and tissue uptake of wild-type 125I-HDL tracer were similar in both genotypes of recipient mice, suggesting that adipocyte ABCA1 deficiency reduces plasma HDL concentrations solely by reducing nascent HDL particle formation. Conclusions— We provide in vivo evidence that AT ABCA1-dependent cholesterol efflux and nascent HDL particle formation contribute to systemic HDL biogenesis and that AT ABCA1 expression plays an important role in adipocyte cholesterol homeostasis. # Clinical Perspective {#article-title-41}
John S Parks - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivo
Circulation, 2011Co-Authors: Abraham K. Gebre, Soonkyu Chung, Janet K Sawyer, Nobuyo Maeda, John S ParksAbstract:Background—Adipose tissue (AT) is the body's largest free cholesterol reservoir and abundantly expresses ATP binding Cassette Transporter A1 (ABCA1), a key cholesterol Transporter for high-density lipoprotein (HDL) biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown. Methods and Results—Adipocyte-specific ABCA1 knockout mice (ABCA1−A/−A) were generated by crossing ABCA1floxed mice with aP2Cre transgenic mice. AT from ABCA1−A/−A mice had <10% of wild-type ABCA1 protein expression but normal hepatic and intestinal expression. Deletion of adipocyte ABCA1 resulted in a significant decrease in plasma HDL cholesterol (≈15%) and apolipoprotein A-I (≈13%) concentrations. AT from ABCA1−A/−A mice had a 2-fold increase in free cholesterol content compared with wild-type mice and failed to efflux cholesterol to apolipoprotein A-I. However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice. Incubation of wild-type AT explants with ...
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adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivoclinical perspective
Circulation, 2011Co-Authors: Soonkyu Chung, Abraham K. Gebre, Janet K Sawyer, Nobuyo Maeda, John S ParksAbstract:Background— Adipose tissue (AT) is the body's largest free cholesterol reservoir and abundantly expresses ATP binding Cassette Transporter A1 (ABCA1), a key cholesterol Transporter for high-density lipoprotein (HDL) biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown. Methods and Results— Adipocyte-specific ABCA1 knockout mice (ABCA1−A/−A) were generated by crossing ABCA1floxed mice with aP2Cre transgenic mice. AT from ABCA1−A/−A mice had <10% of wild-type ABCA1 protein expression but normal hepatic and intestinal expression. Deletion of adipocyte ABCA1 resulted in a significant decrease in plasma HDL cholesterol (≈15%) and apolipoprotein A-I (≈13%) concentrations. AT from ABCA1−A/−A mice had a 2-fold increase in free cholesterol content compared with wild-type mice and failed to efflux cholesterol to apolipoprotein A-I. However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice. Incubation of wild-type AT explants with apolipoprotein A-I resulted in the formation of multiple discrete-sized nascent HDL particles ranging in diameter from 7.1 to 12 nm; similar incubations with ABCA1−A/−A AT explants resulted in nascent HDL <8 nm. Plasma decay and tissue uptake of wild-type 125I-HDL tracer were similar in both genotypes of recipient mice, suggesting that adipocyte ABCA1 deficiency reduces plasma HDL concentrations solely by reducing nascent HDL particle formation. Conclusions— We provide in vivo evidence that AT ABCA1-dependent cholesterol efflux and nascent HDL particle formation contribute to systemic HDL biogenesis and that AT ABCA1 expression plays an important role in adipocyte cholesterol homeostasis. # Clinical Perspective {#article-title-41}
Alan R Tall - One of the best experts on this subject based on the ideXlab platform.
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atp binding Cassette Transporter a7 abca7 binds apolipoprotein a i and mediates cellular phospholipid but not cholesterol efflux
Journal of Biological Chemistry, 2003Co-Authors: Nan Wang, Marie Gerbodgiannone, Patrick Linselnitschke, Andreas W Jehle, Wengen Chen, Laurent O Martinez, Alan R TallAbstract:Abstract ATP-binding Cassette Transporter 1 (ABCA1), the defective Transporter in Tangier disease, binds and promotes cellular cholesterol and phospholipid efflux to apolipoprotein I (apoA-I). Based on a high degree of sequence homology between ABCA1 and ABCA7, a Transporter of unknown function, we investigated the possibility that ABCA7 might be involved in apolipoprotein binding and lipid efflux. Similarly to cells expressing ABCA1, HEK293 cells overexpressing ABCA7 showed specific binding and cross-linking of lipid-poor apoA-I. ABCA7 expression increased cellular phosphatidylcholine and sphingomyelin efflux to apoA-I in a manner similar to ABCA1 but had no effect on cholesterol efflux. Western analysis showed a high protein level of ABCA7 in mouse spleen, lung, adrenal, and brain but low expression in liver. In contrast to ABCA1, ABCA7 showed moderate basal mRNA and protein levels in macrophages and lymphocytes but no induction by liver X receptor activation. These studies show that ABCA7 has the ability to bind apolipoproteins and promote efflux of cellular phospholipids without cholesterol, and they suggest a possible role of ABCA7 in cellular phospholipid metabolism in peripheral tissues.
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atp binding Cassette Transporter a1 abca1 functions as a cholesterol efflux regulatory protein
Journal of Biological Chemistry, 2001Co-Authors: Nan Wang, David L Silver, Christoph Thiele, Alan R TallAbstract:Abstract ABCA1, an ATP-binding Cassette Transporter mutated in Tangier disease, promotes cellular phospholipid and cholesterol efflux by loading free apoA-I with these lipids. This process involves binding of apoA-I to the cell surface and phospholipid translocation by ABCA1. The goals of this study were to examine the relationship between ABCA1-mediated lipid efflux and apolipoprotein binding and to determine whether phospholipid and cholesterol efflux are coupled. Inhibition of lipid efflux by glybenclamide treatment or by mutation of the ATP-binding Cassette of ABCA1 showed a close correlation between lipid efflux, the binding of apoA-I to cells, and cross-linking of apoA-I to ABCA1. The data suggest that a functionally important apoA-I binding site exists on ABCA1 and that the binding site could also involve lipids. After using cyclodextrin preincubation to deplete cellular cholesterol, ABCA1-mediated cholesterol efflux was abolished but phospholipid efflux and the binding of apoA-I were unaffected. The conditioned media from cyclodextrin-pretreated, ABCA1-expressing cells readily promoted cholesterol efflux when added to fresh cells not expressing ABCA1, indicating that cholesterol efflux can be dissociated from phospholipid efflux. Further, using a photoactivatable cholesterol analog, we showed that ABCA1 did not bind cholesterol directly, even though several other cholesterol-binding proteins specifically bound the cholesterol analog. The data suggest that the binding of apoA-I to ABCA1 leads to the formation of phospholipid-apoA-I complexes, which subsequently promote cholesterol efflux in an autocrine or paracrine fashion.
C K Tang - One of the best experts on this subject based on the ideXlab platform.
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effects of oleate on atp binding Cassette Transporter a1 expression and cholesterol efflux in thp 1 macrophage derived foam cells
Acta Biochimica et Biophysica Sinica, 2003Co-Authors: C K Tang, Junhao Yang, Guanghui Yi, Zhugang Wang, Zhonghua Yuan, Changgeng Ruan, Yongzong YangAbstract:Abstract To study the effect of oleate on ATP binding Cassette Transporter A1 (ABCA1) expression and cholesterol efflux in THP-1 macrophage-derived foam cells, after exposure of the cultured THP-1 macrophage-derived foam cells to oleate for different time, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and its protein level were determined by RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity of THP-1 macrophage-derived foam cells was detected by flow cytometry. The results showed that oleate markedly inhibited ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by a reduction in the membrane content of ABCA1. Oleate did not alter ABCA1 mRNA abundance, indicating that decreased ABCA1 transcription, enhanced mRNA decay, or impaired translation efficiency did not account for these inhibitory effects. Oleate, however, increased ABCA1 turnover when protein synthesis was blocked by cycloheximide. Oleate reduces cholesterol efflux and the level of ABCA1 protein in THP-1 macrophage-derived foam cells.
