Critical role of ABCA1 transporter in sphingosine 1-phosphate release from astrocytes
Abstract
Sphingosine 1‐phosphate (S1P) is accumulated in lipoproteins, especially high‐density lipoprotein (HDL), in plasma. However, it remains uncharacterized how extracellular S1P is produced in the CNS. The treatment of rat astrocytes with retinoic acid and dibutyryl cAMP, which induce apolipoprotein E (apoE) synthesis and HDL‐like lipoprotein formation, stimulated extracellular S1P accumulation in the presence of its precursor sphingosine. The released S1P was present together with apoE particles in the HDL fraction. S1P release from astrocytes was inhibited by the treatment of the cells with glybenclamide or small interfering RNAs specific to ATP‐binding cassette transporter A1 (ABCA1). Astrocytes from Abca1−/− mice also showed impairment of retinoic acid/dibutyryl cAMP‐induced S1P release in association with the blockage of HDL‐like lipoprotein formation. However, the formation of either apoE or lipoprotein itself was not sufficient, and additional up‐regulation of ABCA1 was requisite to stimulate S1P release. We conclude that the S1P release from astrocytes is coupled with lipoprotein formation through ABCA1.
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S1P is involved in HDL function and neuroinflammation through regulation of gene expression in the nucleus and alteration in the functioning of various immune cells.
“The signaling lipid S1P is involved in high-density lipoprotein (HDL) function (44) and neuroinflammation through the regulation of gene expression in the nucleus and alteration in the functioning of various immune cells (45).”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [44]
S1P is incorporated into HDL-like particles in an ABCA1-dependent manner and coexists with ApoE.
“S1P is incorporated into HDL-like particles in an ABCA1-dependent manner and coexists with ApoE (44)”
From Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes (2024) · cites this paper as [44]
Cites
Role of ABCC1 in export of sphingosine-1-phosphate from mast cells
Mitra, P., Oskeritzian, C. A., Payne, S. G., Beaven, M. A., Milstien, S., & Spiegel, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603734103 · Cited by 407 · see citing works
Nascent astrocyte particles differ from lipoproteins in CSF
LaDu, M. J., Gilligan, S. M., Lukens, J. R., Cabana, V. G., Reardon, C. A., Van Eldik, L. J., & Holtzman, D. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052070.x · Cited by 285 · see citing works
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An update on the biology of sphingosine 1-phosphate receptors
Blaho, V. A., & Hla, T. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r046300 · Cited by 516 · see citing works
Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion
Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J., & Zorec, R. (2016) · The EMBO Journal · doi:10.15252/embj.201592705 · Cited by 397 · see citing works
Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes
Komai, M., Noda, Y., Ikeda, A., Kaneshiro, N., Kamikubo, Y., Sakurai, T., Uehara, T., & Takasugi, N. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100510 · Cited by 13 · see citing works
- Authors
- Sato, K., Malchinkhuu, E., Horiuchi, Y., Mogi, C., Tomura, H., Tosaka, M., Yoshimoto, Y., Kuwabara, A., & Okajima, F.
- Affiliations
- Gunma University (JP)
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-09-14
- Volume
- 103
- Issue
- 6
- Pages
- 2610-2619
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2062029352
- Cited by
- 183
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 12 · 2016: 9 · 2015: 13 · 2014: 14 · 2013: 21 · 2012: 20
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- sphingosine-1-phosphate, ABCA1, astrocytes, apolipoprotein E, ABC transporters, retinoic acid, dibutyryl cyclic AMP, glibenclamide
- MeSH terms
- Adenoviridae, Animals, Apolipoproteins E, Astrocytes, Cell Movement, Cells, Cultured, Bucladesine, Genetic Vectors, Lipoproteins, Lipoproteins, HDL, Lysophospholipids, Mice, Inbred DBA, Sphingosine, Stimulation, Chemical, Tretinoin, Blotting, Western, Culture Media, Conditioned, Mice, Knockout, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
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