Iron-dependent lysosomal LDL oxidation induces the expression of scavenger receptor A in human THP-1 monocytes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10498458" target="_blank" >RIV/00216208:11110/25:10498458 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ET2lv3Fqr0" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ET2lv3Fqr0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/2211-5463.70048" target="_blank" >10.1002/2211-5463.70048</a>
Alternative languages
Result language
angličtina
Original language name
Iron-dependent lysosomal LDL oxidation induces the expression of scavenger receptor A in human THP-1 monocytes
Original language description
Atherosclerosis leading to cardiovascular diseases remains a dominant medical problem. In the early stages of this disease, the interaction between circulating monocytes and the endothelium is crucial. Monocytes and macrophages express scavenger receptor A (SR-A), which mediates cell adhesion and subsequently uptake of oxidized low-density lipoproteins (LDL). High iron stores in monocytes or macrophages are known to predispose individuals to atherosclerosis, however the reasons remain poorly understood. We hypothesized that a combination of iron and LDL may induce proatherogenic changes in circulating monocytes. Here, we treated a human monocytic cell line THP-1 with isolated LDL and/or iron. A limited uptake of native LDL, but not iron or oxidized LDL, markedly induced expression of SR-A in these cells. Both SR-AI and SR-AII isoforms were upregulated. The increased SR-A was also seen at the protein level, and LDL treatment increased cellular adhesion. The induction of SR-A by LDL was inhibited by the lysosomotropic thiol WR-1065 and by the chain-breaking lipophilic antioxidant butylated hydroxytoluene (BHT). The fluorescent probe BODIPY C11 exhibited increased lipid peroxidation inside lysosomes after LDL administration. The induction of SR-A by LDL was blocked by two silencing RNAs directed against the nuclear coactivator receptor NCOA4, the cargo receptor necessary for the autophagy of ferritin. These results may point to a new pathogenetic mechanism of early-stage atherosclerosis, in which high iron stores in circulating monocytes, through increased lysosomal lipid peroxidation, may lead to an upregulated expression of SR-A, which makes the cells more adhesive and hence more atherogenic.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30202 - Endocrinology and metabolism (including diabetes, hormones)
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
FEBS Open Bio
ISSN
2211-5463
e-ISSN
2211-5463
Volume of the periodical
15
Issue of the periodical within the volume
8
Country of publishing house
GB - UNITED KINGDOM
Number of pages
21
Pages from-to
1246-1266
UT code for WoS article
001484894400001
EID of the result in the Scopus database
2-s2.0-105004771688