Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum

Yamauchi, Yoshio; Iwamoto, Noriyuki; Rogers, Maximillian A.; Abe-Dohmae, Sumiko; Fujimoto, Toyoshi; Chang, Catherine C.Y.; Ishigami, Masato; Kishimoto, Tadamitsu; Kobayashi, Toshihide; Ueda, Kazumitsu; Furukawa, Koichi; Chang, Ta−Yuan; Yokoyama, Shinji

doi:10.1074/jbc.m115.662668

Cited by 59 publications

(68 citation statements)

References 70 publications

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“…Cells (CHO, HEK293, HSFs, and MEFs) were seeded into 6-well plates, as described ( 7,17,18 ). HSFs and MEFs were pretreated or not pretreated with 9cRA (RXR ligand) and/or the synthetic LXR agonist, TO901317, as indicated in the fi gure legends, to induce ABCA1 expression.…”

Section: Sterol Release Assaysmentioning

confidence: 99%

“…Briefl y, the PNS was mixed with OptiPrep or with 80% sucrose (in TNE buffer) to be at 37.5 or 40% as a fi nal concentration, respectively, and placed at the bottom of an ultracentrifuge tube. Optiprep (30%) or sucrose (30%) were layered and TNE buffer or 5% sucrose was then layered on the to cholesterol ( 17,18 ). Circulating lipoproteins such as HDL contain small, but signifi cant, amounts of various precursor sterols, including lanosterol and other methylated sterols (i.e., C28, C29, and C30 sterols) ( 19 ).…”

Section: Cell Fractionationmentioning

confidence: 99%

“…Mouse embryonic fi broblasts (MEFs) from Abca1 +/+ (WT) and Abca1 Ϫ / Ϫ mice were isolated and used for experiments, as previously described ( 18,39 ). HEK293 cells stably expressing human ABCA1 (clone 293/2c, hereafter referred as to HEK/hABCA1) were established previously ( 40 ).…”

Section: Cell Culture and Mediamentioning

confidence: 99%

“…Therefore, the preferential release of lanosterol by ABCA1-mediated HDL biogenesis may provide a means to limit the build-up of lanosterol. We recently reported that ABCA1 also facilitates PM-to-ER lanosterol movement for its conversion to cholesterol ( 18 ). At the ER, lanosterol is fi rst converted to Fig.…”

Section: Downloaded Frommentioning

confidence: 99%

“…Some of the HSF lines used here were employed in our previous study ( 17 ). HSFs and MEFs were grown in DMEM with penicillin and streptomycin supplemented with 10% FBS ( 17,18 ). The human monocyte-like THP-1 cells were differentiated to macrophage-like cells by using the procedure described in ( 43 ).…”

mentioning

confidence: 99%

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ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

Yamauchi

Yokoyama

Chang

2016

Journal of Lipid Research

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Section: Sterol Release Assaysmentioning

confidence: 99%

Section: Cell Fractionationmentioning

confidence: 99%

Section: Cell Culture and Mediamentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

mentioning

confidence: 99%

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ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

Yamauchi

Yokoyama

Chang

2016

Journal of Lipid Research

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Implantable Electroceutical Approach Improves Myelination by Restoring Membrane Integrity in a Mouse Model of Peripheral Demyelinating Neuropathy

et al. 2022

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Although many efforts are undertaken to treat peripheral demyelinating neuropathies based on biochemical interventions, unfortunately, there is no approved treatment yet. Furthermore, previous studies have not shown improvement of the myelin membrane at the biomolecular level. Here, an electroceutical treatment is introduced as a biophysical intervention to treat Charcot-Marie-Tooth (CMT) disease-the most prevalent peripheral demyelinating neuropathy worldwide-using a mouse model. The specific electrical stimulation (ES) condition (50 mV mm −1 , 20 Hz, 1 h) for optimal myelination is found via an in vitro ES screening system, and its promyelinating effect is validated with ex vivo dorsal root ganglion model. Biomolecular investigation via time-of-flight secondary ion mass spectrometry shows that ES ameliorates distribution abnormalities of peripheral myelin protein 22 and cholesterol in the myelin membrane, revealing the restoration of myelin membrane integrity. ES intervention in vivo via flexible implantable electrodes shows not only gradual rehabilitation of mouse behavioral phenotypes (balance and endurance), but also restored myelin thickness, compactness, and membrane integrity. This study demonstrates, for the first time, that an electroceutical approach with the optimal ES condition has the potential to treat CMT disease and restore impaired myelin membrane integrity, shifting the paradigm toward practical interventions for peripheral demyelinating neuropathies.

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Methods for Monitoring ABCA1-Dependent Sterol Release

Yamauchi

Yokoyama

Chang

2017

Methods in Molecular Biology

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Releasing sterols to the extracellular milieu is an important part of sterol homeostasis in cells and in the body. ATP-binding cassette transporter Al (ABCA1) plays an essential role in cellular phospholipid and sterol release to lipid-free or lipid-poor apolipoprotein A-I (apoA-I), the major apolipoprotein in high-density lipoprotein (HDL), and constitutes the first step in the formation of nascent HDL. Loss-of-function mutations in the ABCA1 gene lead to a rare disease known as Tangier disease that causes severe deficiency in plasma HDL level. Mammalian cells receive exogenous cholesterol mainly from low-density lipoprotein. In addition, they synthesize cholesterol endogenously, as well as multiple precursor sterols that are sterol intermediates en route to be converted to cholesterol. HDL contains phospholipids, cholesterol, and precursor sterols, and ABCA1 has an ability to release phospholipids and various sterol molecules. Recent studies using model cell lines showed that ABCA1 prefers to use sterols newly synthesized endogenously as its preferred substrate, rather than cholesterol derived from LDL or cholesterol being recycled within the cells. Here, we describe several methods at the cell culture level to monitor ABCA1-dependent release of sterol molecules to apoA-I present at the cell exterior. Sterol release can be assessed by using a simple colorimetric enzymatic assay, and/or by monitoring the radioactivities of radiolabeled cholesterol incorporated into the cells, and/or of sterols biosynthesized from radioactive acetate, and/or by using gas chromatography-mass spectrometry analysis of various sterols present in medium and in cells. We also discuss the pros and cons of these methods. Together, these methods allow researchers to detect the release not only of cholesterol but also of other sterols present in minor quantities.

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Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum

Cited by 59 publications

References 70 publications

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

Implantable Electroceutical Approach Improves Myelination by Restoring Membrane Integrity in a Mouse Model of Peripheral Demyelinating Neuropathy

Methods for Monitoring ABCA1-Dependent Sterol Release

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