CoChat
Sign Up
Cited by 214Cholesterol and Lipid MetabolismAlzheimer's disease research and treatmentsLipoproteins and Cardiovascular Health

Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice

Open access
Gong, Jian-Sheng, Kobayashi, Mariko, Hayashi, Hideki, Zou, Kun, Sawamura, Naoya, Fujita, Shinobu C., Yanagisawa, Katsuhiko, Michikawa, Makoto·2002·Journal of Biological Chemistry
DOI 10.1074/jbc.m203934200
Open this paper in CoChat — free accountOpen PDF

Abstract

We have reported previously (Michikawa, M., Fan, Q.-W., Isobe, I., and Yanagisawa, K. (2000) J. Neurochem. 74, 1008-1016) that exogenously added recombinant human apolipoprotein E (apoE) promotes cholesterol release in an isoform-dependent manner. However, the molecular mechanism underlying this isoform-dependent promotion of cholesterol release remains undetermined. In this study, we demonstrate that the cholesterol release is mediated by endogenously synthesized and secreted apoE isoforms and clarify the mechanism underlying this apoE isoform-dependent cholesterol release using cultured astrocytes prepared from human apoE3 and apoE4 knock-in mice. Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. The amount of cholesterol released into the culture media from the apoE3-expressing astrocytes was approximately 2.5-fold greater than that from apoE4-expressing astrocytes. In contrast, the amount of apoE3 released in association with the HDL-like particles was similar to that of apoE4, and the sizes of the HDL-like particles released from apoE3- and apoE4-expressing astrocytes were similar. The molar ratios of cholesterol to apoE in the HDL fraction of the culture media of apoE3- and apoE4-expressing astrocytes were 250 +/- 6.0 and 119 +/- 5.1, respectively. These data indicate that apoE3 has an ability to generate similarly sized lipid particles with less number of apoE molecules than apoE4, suggesting that apoE3-expressing astrocytes can supply more cholesterol to neurons than apoE4-expressing astrocytes. These findings provide a new insight into the issue concerning the putative alteration of apoE-related cholesterol metabolism in Alzheimer's disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m203934200

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In the central nervous system, apoE is mainly secreted by astrocytes, with different isoforms playing distinct roles in lipid metabolism and nervous system homeostasis.

    “In the central nervous system (CNS), apoE is mainly secreted by astrocytes, with different isoforms playing distinct roles in lipid metabolism and nervous system homeostasis [11, 12].”

    From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [12]

    The Discussion (page not provided) reports that apoE3-expressing astrocytes release more lipid than apoE4-expressing astrocytes and suggests a resulting difference in cholesterol supply to neurons, supporting the isoform-dependent lipid-metabolism point. The Results (page not provided) show apoE release from cultured astrocytes, but the paper does not establish that astrocytes are the main source of secreted apoE throughout the CNS. Its proposed effects on neuronal plasticity and regeneration are narrower than a general claim about nervous system homeostasis. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Cholesterol release is reduced in primary glial cultures from apoE-TR mice expressing apoE4 compared with glial cells expressing apoE3.

    “cholesterol release is reduced in primary glial cultures from apoE-TR mice expressing apoE4 compared with glial cells expressing apoE3 (35,73).”

    From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [73]

  • ApoE4 proteins are poorly lipidated and display an impaired capacity in lipid transport when compared to apoE3 proteins.

    “apoE4 proteins are poorly lipidated and display an impaired capacity in lipid transport when compared to apoE3 proteins”

    From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Gong et al 2002

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., and Simons, K. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 6460 -6464
  2. Fassbender, K., Simons, M., Bergmann, C., Stroick, M., Lutjohann, D., Keller, P., Runz, H., Kuhl, S., Bertsch, T., von Bergmann, K., Hennerici, M., Beyreuther, K., and Hartmann, T. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 5856 -5861
  3. Liu, Y., Peterson, D. A., and Schubert, D. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13266 -13271
  4. Gong, J. S., Sawamura, N., Zou, K., Sakai, J., Yanagisawa, K., and Michikawa, M. (2002) J. Neurosci. Res., in press
  5. Roheim, P. S., Carey, M., Forte, T., and Vega, G. L. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 4646 -4649
  6. Huang, Y., von Eckardstein, A., Wu, S., Maeda, N., and Assmann, G. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 1834 -1838
  7. Raffai, R. L., Dong, L. M., Farese, R. V., Jr., and Weisgraber, K. H. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11587-11591

Cited by

Sorted by citations

Related

Authors
Gong, J.-S., Kobayashi, M., Hayashi, H., Zou, K., Sawamura, N., Fujita, S. C., Yanagisawa, K., & Michikawa, M.
Affiliations
Japan Society for the Promotion of Science (JP)
Corresponding author
Michikawa, Makoto
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-08
Volume
277
Issue
33
Pages
29919-29926
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m203934200
OpenAlex
W2087083058
Cited by
214
References
68
Citations by year
2026: 5 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 11 · 2019: 13 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 6
FWCI
10.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein E, APOE isoforms, APOE3, APOE ε4, astrocytes, lipid secretion, clusterin, cholesterol metabolism, Alzheimer's disease
MeSH terms
Animals, Apolipoproteins E, Astrocytes, Cells, Cultured, Humans, Protein Isoforms, Lipid Metabolism, Mice, Apolipoprotein E3, Apolipoprotein E4

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review