CoChat
Sign Up
Cited by 668Cholesterol and Lipid MetabolismSteroid Chemistry and BiochemistryPharmacogenetics and Drug Metabolism

cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain

Open access
Lund, Erik G., Guileyardo, Joseph M., Russell, David W.·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.13.7238PMC PMC22064
Open this paper in CoChat — free account

Abstract

The turnover of cholesterol in the brain is thought to occur via conversion of excess cholesterol into 24S-hydroxycholesterol, an oxysterol that is readily secreted from the central nervous system into the plasma. To gain molecular insight into this pathway of cholesterol metabolism, we used expression cloning to isolate cDNAs that encode murine and human cholesterol 24-hydroxylases. DNA sequence analysis indicates that both proteins are localized to the endoplasmic reticulum, share 95% identity, and represent a new cytochrome P450 subfamily (CYP46). When transfected into cultured cells, the cDNAs produce an enzymatic activity that converts cholesterol into 24S-hydroxycholesterol, and to a lesser extent, 25-hydroxycholesterol. The cholesterol 24-hydroxylase gene contains 15 exons and is located on human chromosome 14q32.1. Cholesterol 24-hydroxylase is expressed predominantly in the brain as judged by RNA and protein blotting. In situ mRNA hybridization and immunohistochemistry localize the expression of this P450 to neurons in multiple subregions of the brain. The concentrations of 24S-hydroxycholesterol in serum are low in newborn mice, reach a peak between postnatal days 12 and 15, and thereafter decline to baseline levels. In contrast, cholesterol 24-hydroxylase protein is first detected in the brain of mice at birth and continues to accumulate with age. We conclude that the cloned cDNAs encode cholesterol 24-hydroxylases that synthesize oxysterols in neurons of the brain and that secretion of 24S-hydroxycholesterol from this tissue in the mouse is developmentally regulated.

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 · 10.1073/pnas.96.13.7238

Cites

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?

  • Oxysterols can pass lipophilic membranes more easily than cholesterol, allowing for one-way egress across the BBB and into the body.

    “Oxysterols can pass lipophilic membranes more easily than cholesterol, allowing for one-way egress across the BBB and into the body [163].”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [163]

    The Discussion (page unavailable) says that 24S-hydroxycholesterol is readily secreted across the blood–brain barrier into circulation and then taken up by the liver. It does not establish that oxysterols generally cross lipophilic membranes more easily than cholesterol, or that passage across the barrier is one-way. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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

No references could be resolved yet.

Research works printed but not linked: 7

  1. [4]Bjo ¨rkhem, I., Andersson, O., Diczfalusy, U., Sevastik, B., Xiu, R., Duan, C. & Lund, E. (1994) Proc. Natl. Acad. Sci. USA 91, 8592-8596.
  2. [8]Lu ¨tjohann, D., Breuer, O., Ahlborg, G., Nennesmo, I., Siden, A., Diczfalusy, U. & Bjo ¨rkhem, I. (1996) Proc. Natl. Acad. Sci. USA 93, 9799-9804.
  3. [15]Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY), 2nd Ed.
  4. [18]Harlow, E. & Lane, D. (1988) Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY).
  5. [19]Hogan, B., Beddington, R., Costantini, F. & Lacy, E. (1995) Manipulating The Mouse Embryo (Cold Spring Harbor Lab. Press, Plainview, NY).
  6. [20]Berman, D. M. & Russell, D. W. (1993) Proc. Natl. Acad. Sci. USA 90, 9359-9363.
  7. [30]Susuki, K. (1976) in Basic Neurochemistry , eds. Siegel, G. J., Albers, R. W., Katzman, R. & Agranoff, B. W. (Little, Brown, Boston), pp. 308-328.

Cited by

Sorted by citations

Authors
Lund, E. G., Guileyardo, J. M., & Russell, D. W.
Affiliations
The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-06-22
Volume
96
Issue
13
Pages
7238-7243
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.13.7238
PMC
PMC22064
OpenAlex
W2081722421
Cited by
668
References
0
Citations by year
2026: 16 · 2025: 25 · 2024: 26 · 2023: 30 · 2022: 31 · 2021: 28 · 2020: 32 · 2019: 23 · 2018: 16 · 2017: 16 · 2016: 21 · 2015: 24 · 2014: 35 · 2013: 27 · 2012: 33
FWCI
19.34
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Welch Foundation (I-0971)
  • Direktør Throne Holsts Fond For Ernæringsforskning
  • National Institutes of Health (HL20948)
  • National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
cholesterol 24-hydroxylase, cholesterol homeostasis, brain, 24S-hydroxycholesterol, oxysterols, 25-hydroxycholesterol, cytochrome P450, endoplasmic reticulum, neurons, developmental regulation, gene expression
MeSH terms
Amino Acid Sequence, Animals, Brain, Cholesterol, Cloning, Molecular, Cytochrome P-450 Enzyme System, Homeostasis, Humans, Molecular Sequence Data, Organ Specificity, Steroid Hydroxylases, Sequence Alignment, DNA, Complementary, Mice

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