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ATP-binding Cassette Transporter

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Yongzong Yang – 1st expert on this subject based on the ideXlab platform

  • 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, 2003
    Co-Authors: C K Tang, Junhao Yang, Guanghui Yi, Zhugang Wang, Zhonghua Yuan, Changgeng Ruan, Yongzong Yang

    Abstract:

    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 – 2nd expert on this subject based on the ideXlab platform

  • adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivo
    Circulation, 2011
    Co-Authors: Abraham K. Gebre, Soonkyu Chung, Janet K Sawyer, Nobuyo Maeda, John S Parks

    Abstract:

    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 ...

  • adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivoclinical perspective
    Circulation, 2011
    Co-Authors: Soonkyu Chung, Abraham K. Gebre, Janet K Sawyer, Nobuyo Maeda, John S Parks

    Abstract:

    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 – 3rd expert on this subject based on the ideXlab platform

  • adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivo
    Circulation, 2011
    Co-Authors: Abraham K. Gebre, Soonkyu Chung, Janet K Sawyer, Nobuyo Maeda, John S Parks

    Abstract:

    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 ...

  • adipose tissue atp binding Cassette Transporter a1 contributes to high density lipoprotein biogenesis in vivoclinical perspective
    Circulation, 2011
    Co-Authors: Soonkyu Chung, Abraham K. Gebre, Janet K Sawyer, Nobuyo Maeda, John S Parks

    Abstract:

    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}