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Cited by 45Cholesterol and Lipid MetabolismDrug Transport and Resistance MechanismsLipoproteins and Cardiovascular Health

LRP1 Controls cPLA2 Phosphorylation, ABCA1 Expression and Cellular Cholesterol Export

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Zhou, Li, Choi, Hong Y., Li, Wei-Ping, Xu, Fang, Herz, Joachim·2009·PLoS ONE
DOI 10.1371/journal.pone.0006853PMC PMC2729921
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Abstract

BACKGROUND: ATP-binding cassette transporter A1 mediates apolipoprotein AI-dependent efflux of cholesterol and thereby removes cholesterol from peripheral tissues. ABCA1 expression is tightly regulated and deficiency of this cholesterol transporter results in cholesterol accumulation within cells. Low-density lipoprotein receptor-related protein 1 (LRP1) participates in lipid metabolism and energy homeostasis by endocytosis of apolipoprotein E-containing lipoproteins and modulation of cellular proliferation signals. METHODS AND PRINCIPAL FINDINGS: In the present study, we demonstrate a new role for LRP1 in reverse cholesterol transport. Absence of LRP1 expression results in increased PDGFRbeta signaling and sequential activation of the mitogen-activated protein kinase signaling pathway, which increases phosphorylation of cytosolic phospholipase A(2) (cPLA(2)). Phosphorylated and activated cPLA(2) releases arachidonic acid from the phospholipid pool. Overproduction of arachidonic acid suppresses the activation of LXR/RXR heterodimers bound to the promoter of LXR regulated genes such as ABCA1, resulting in greatly reduced ABCA1 expression. CONCLUSIONS AND SIGNIFICANCE: LRP1 regulates LXR-mediated gene transcription and participates in reverse cholesterol transport by controlling cPLA(2) activation and ABCA1 expression. LRP1 thus functions as a physiological integrator of cellular lipid homeostasis with signals that regulate cellular proliferation and vascular wall integrity.

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  • LRP1 is known to control cPLA2 activation and the consequent intracellular levels of AA via the MAPK signaling pathway.

    “While LRP1 is known to control cPLA2 activation and the consequent intracellular levels of AA via the MAPK signaling pathway (53)”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [53]

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References 50 · Cited by 45

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Authors
Zhou, L., Choi, H. Y., Li, W.-P., Xu, F., & Herz, J.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Herz, Joachim
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-08-31
Volume
4
Issue
8
Pages
e6853
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0006853
PMC
PMC2729921
OpenAlex
W2015270219
Cited by
45
References
50
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 6
FWCI
4.39
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Heart Association (HL20948)
  • Alexander von Humboldt-Stiftung
  • National Institutes of Health (HL20948, HL63762)
  • National Heart, Lung, and Blood Institute (HL-20948, R01HL063762, HL63762, R37HL063762, P01HL020948)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
LRP1, cytosolic phospholipase A2, ABCA1, reverse cholesterol transport, cholesterol efflux, arachidonic acid, PDGFRβ signaling, MAPK signaling, lipid homeostasis, apolipoprotein A-I, apolipoprotein E, transcriptional regulation
MeSH terms
Animals, Base Sequence, Biological Transport, Cholesterol, Chromatography, Thin Layer, Mice, Inbred C57BL, Microscopy, Fluorescence, Phosphorylation, Receptors, LDL, Transcription, Genetic, Blotting, Western, Polymerase Chain Reaction, DNA Primers, Mice, Knockout, ATP-Binding Cassette Transporters, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Phospholipases A2, ATP Binding Cassette Transporter 1

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